Table 1

Filtered variants for families PSYAK2 and PSYAK3 after exome sequencing

Aggregated allele frequency, %Predictions
Family IDGenegDNA change*RefSeq IDcDNA change and amino acid changegnomADFrom 300 ethnically matched controlsConservation GERPCADDSIFTPolyPhen2REVELMTFATHMMSpliceAl
PSYAK2OR13C2Chr9: 107367821
G > C
NM_001004481.1c.88C > G p.Leu30Val, missense0.0002781 (0 homozygous)0.001671.458.1290.09
T
0.03
B
0
B
0.03
B
2.32
T
0.03
B
RGS3Chr9: 116247933
C > T
NM_144488.5c.649C > T p.Arg217Cys, missense0.00004903 (0 homozygous)04.66320
D
1
D
0.62
D
0.99
D
−1.07
B
0.13
U
NR6A1Chr9: 127287141 G > ANM_033334.4c.1213C > T p.Leu405Leu, synonymous0.0006331 (0 homozygous)0NA11.49NANANANANANA
GAPVD1Chr9: 128117939 C > TNM_001282680.2c.3774C > T p.Thr1258Thr, synonymous0.0001516 (0 homozygous)0.00167NA8.623NANANANANANA
HMCN2Chr9: 133224403 C > TNM_001291815.2c.2514C > T p.Asp838Asp, synonymous0.0014 (1 homozygous)0.01NA0.231NANANANANANA
MED27Chr9: 134735938
G > A
NM_004269.4c.923C > T p.Thr308Ile, missense0.0002064 (1 homozygous)05.323.30.06
T
0.11
B
0.24
B
1
D
NA0
B
SETXChr9: 135202835
A > T
NM_015046.7c.4150T > A p.Ser1384Thr, missense0.0001352 (0 homozygous)0.00167−0.186.7140.02
D
0.09
B
0.27
B
0
B
−2.19
D
0
B
FLI1§Chr11: 128651917 A > GNM_002017.5c.654 A > G
p.Glu218Glu, synonymous
0.0002607
(1 homozygous)
0.002NA21.1NANANANANA0.01
D
SNX19Chr11: 130749601
C > T
NM_014758.2c.2764G > A p.Val922Ile, missense0.00001593 (0 homozygous)0−2.380.1270.46
T
0.05
B
0.02
B
0
B
1.55
T
0
B
PSYAK3WDR33Chr2: 128477570
T > C
NM_018383.5c.2029A > G p.Met677Val, missense0.0001316 (0 homozygous)0.0067−0.1418.220.06
T
NA0.1
B
0.66
D
2.55
T
0
B
CD44Chr11: 35160895 G > CNM_000610.3c.45G > C p.Val15Val, synonymous0.0008269 (2 homozygous)0.01NA14.61NANANANANANA
STX3Chr 11: 59557993
C > T
NM_004177.5c.291C > T p.Ser97Ser, synonymous0.001515 (2 homozygous)0.015NA14.77NANANANANA0
B
ROM1Chr11: 62380834 G > TNM_000327.3c.81G > T p.Leu27Leu, synonymous0.001259 (0 homozygous)0.0033NA0.699NANANANANANA
C11ORF95Chr11: 63531586 G > ANM_001144936.2c.1509C > T p.Pro503Pro, synonymous0.0008351 (0 homozygous)0.005NA5.782NANANANANANA
TRIM64BChr11: 89608155 A > GNM_001164397.2c.495T > C p.His165His, synonymous0.0002230 (0 homozygous)0.00167NA0.325NANANANANANA
IL1RAPL1ChrX: 29417422
A > G
NM_014271.3c.700A > G p.Thr234Ala, missense0.000005491 (1 hemizygous)05.7523.80.08
T
NA0.52
D
1
D
−1.07
T
0
B
  • B = benign; CADD = Combined Annotation Dependent Depletion (higher scores are more damaging); D = damaging or deleterious; GERP = Genomic Evolutionary Rate Prediction; gnomAD = Genome Aggregation Database; FATHMM = Functional Annotation Through Hidden Markov Models; MT = Mutation Taster; NA = not applicable; PolyPhen2 = Polymorphism Phenotyping v2; RefSeq = Reference Sequence; REVEL = Rare Exome Variant Ensemble Learner; SIFT = Sorting Intolerant from Tolerant algorithm; SpliceAI = Splice Altering algorithm; T = tolerated; U = uncertain.

  • * Variant position according to Human Feb.2009 (GRCh37/hg19) Assembly.

  • RGS3 and IL1RAPL1 variants were absent from the in-house exome data of at least 300 ethnically matched controls and from the DNA of a further 100 individuals analyzed.

  • Negative and low scores indicate no or low conservation.

  • § In family PSYAK2, the FLI1 synonymous variant was predicted to affect splicing. However, the involved nucleotide was not conserved in evolution and had an allele frequency of 0.002 in South Asians, making it unlikely that it would be pathogenic.