rs756836341
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2
The NM_005765.3(ATP6AP2):āc.922A>Cā(p.Asn308His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000331 in 1,207,869 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_005765.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000893 AC: 10AN: 111944Hom.: 0 Cov.: 23 AF XY: 0.000146 AC XY: 5AN XY: 34132
GnomAD3 exomes AF: 0.0000709 AC: 13AN: 183258Hom.: 0 AF XY: 0.0000295 AC XY: 2AN XY: 67748
GnomAD4 exome AF: 0.0000274 AC: 30AN: 1095925Hom.: 0 Cov.: 29 AF XY: 0.00000830 AC XY: 3AN XY: 361405
GnomAD4 genome AF: 0.0000893 AC: 10AN: 111944Hom.: 0 Cov.: 23 AF XY: 0.000146 AC XY: 5AN XY: 34132
ClinVar
Submissions by phenotype
Syndromic X-linked intellectual disability Hedera type Uncertain:1
This sequence change replaces asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 308 of the ATP6AP2 protein (p.Asn308His). This variant is present in population databases (rs756836341, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with ATP6AP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 380358). Invitae Evidence 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 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 ATP6AP2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at