rs143142641
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_012463.4(ATP6V0A2):c.1486G>A(p.Ala496Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000747 in 1,614,146 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_012463.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATP6V0A2 | NM_012463.4 | c.1486G>A | p.Ala496Thr | missense_variant | Exon 12 of 20 | ENST00000330342.8 | NP_036595.2 | |
ATP6V0A2 | XM_024448910.2 | c.1486G>A | p.Ala496Thr | missense_variant | Exon 12 of 19 | XP_024304678.1 | ||
ATP6V0A2 | XM_024448911.2 | c.973G>A | p.Ala325Thr | missense_variant | Exon 8 of 16 | XP_024304679.1 | ||
ATP6V0A2 | XM_024448912.2 | c.664G>A | p.Ala222Thr | missense_variant | Exon 5 of 13 | XP_024304680.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000519 AC: 79AN: 152136Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00118 AC: 296AN: 251486Hom.: 4 AF XY: 0.00145 AC XY: 197AN XY: 135916
GnomAD4 exome AF: 0.000771 AC: 1127AN: 1461892Hom.: 13 Cov.: 33 AF XY: 0.000986 AC XY: 717AN XY: 727248
GnomAD4 genome AF: 0.000512 AC: 78AN: 152254Hom.: 0 Cov.: 32 AF XY: 0.000685 AC XY: 51AN XY: 74444
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:4
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ATP6V0A2: BP4, BS2 -
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not specified Benign:1
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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. -
ATP6V0A2-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
ALG9 congenital disorder of glycosylation Benign:1
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Cutis laxa with osteodystrophy Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at