chr10-101023988-C-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PS1PM2PP3_StrongPP5_Moderate
The NM_001195263.2(PDZD7):c.307G>A(p.Gly103Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,614,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another nucleotide change resulting in same amino acid change has been previously reported as Pathogenicin Lovd.
Frequency
Consequence
NM_001195263.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PDZD7 | NM_001195263.2 | c.307G>A | p.Gly103Arg | missense_variant | 3/17 | ENST00000619208.6 | NP_001182192.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PDZD7 | ENST00000619208.6 | c.307G>A | p.Gly103Arg | missense_variant | 3/17 | 5 | NM_001195263.2 | ENSP00000480489 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152258Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251464Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135902
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461892Hom.: 0 Cov.: 35 AF XY: 0.00000963 AC XY: 7AN XY: 727248
GnomAD4 genome AF: 0.0000591 AC: 9AN: 152376Hom.: 0 Cov.: 32 AF XY: 0.0000268 AC XY: 2AN XY: 74512
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 28, 2022 | This missense change has been observed in individual(s) with deafness (PMID: 26416264). It has also been observed to segregate with disease in related individuals. For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PDZD7 protein function. This variant is present in population databases (rs148695069, gnomAD 0.008%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 103 of the PDZD7 protein (p.Gly103Arg). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at