chr12-123724781-G-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS1_Supporting
The NM_012463.4(ATP6V0A2):c.422G>T(p.Arg141Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000382 in 1,613,336 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R141H) has been classified as Uncertain significance.
Frequency
Consequence
NM_012463.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP6V0A2 | NM_012463.4 | c.422G>T | p.Arg141Leu | missense_variant | 4/20 | ENST00000330342.8 | |
ATP6V0A2 | XM_024448910.2 | c.422G>T | p.Arg141Leu | missense_variant | 4/19 | ||
ATP6V0A2 | XM_024448911.2 | c.-3G>T | 5_prime_UTR_variant | 1/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP6V0A2 | ENST00000330342.8 | c.422G>T | p.Arg141Leu | missense_variant | 4/20 | 1 | NM_012463.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000197 AC: 30AN: 152040Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.000290 AC: 73AN: 251460Hom.: 1 AF XY: 0.000294 AC XY: 40AN XY: 135896
GnomAD4 exome AF: 0.000402 AC: 587AN: 1461296Hom.: 3 Cov.: 31 AF XY: 0.000396 AC XY: 288AN XY: 726984
GnomAD4 genome ? AF: 0.000197 AC: 30AN: 152040Hom.: 0 Cov.: 30 AF XY: 0.000135 AC XY: 10AN XY: 74260
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:2
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 02, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2021 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 17, 2016 | A variant of uncertain significance has been identified in the ATP6V0A2 gene. The R141L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R141L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In addition, this substitution occurs at a position that is conserved across species, and 2/3 in silico algorithms predict this variant is probably damaging to the protein structure/function. However, to our knowledge no studies have been performed to determine the functional effect of the R141L variant.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign. - |
Cutis laxa with osteodystrophy;C0406587:Wrinkly skin syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 10, 2022 | - - |
Cutis laxa with osteodystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
ALG9 congenital disorder of glycosylation Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at