rs372842500
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001692.4(ATP6V1B1):c.422C>T(p.Ala141Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000502 in 1,614,112 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. A141A) has been classified as Likely benign.
Frequency
Consequence
NM_001692.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP6V1B1 | NM_001692.4 | c.422C>T | p.Ala141Val | missense_variant | 5/14 | ENST00000234396.10 | |
ATP6V1B1 | XM_011532907.3 | c.542C>T | p.Ala181Val | missense_variant | 4/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP6V1B1 | ENST00000234396.10 | c.422C>T | p.Ala141Val | missense_variant | 5/14 | 1 | NM_001692.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152108Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000637 AC: 16AN: 251340Hom.: 0 AF XY: 0.0000810 AC XY: 11AN XY: 135824
GnomAD4 exome AF: 0.0000438 AC: 64AN: 1461886Hom.: 0 Cov.: 32 AF XY: 0.0000564 AC XY: 41AN XY: 727242
GnomAD4 genome AF: 0.000112 AC: 17AN: 152226Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74432
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 15, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 141 of the ATP6V1B1 protein (p.Ala141Val). This variant is present in population databases (rs372842500, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ATP6V1B1-related conditions. ClinVar contains an entry for this variant (Variation ID: 504550). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 28, 2021 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533) - |
Renal tubular acidosis with progressive nerve deafness Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Mar 09, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 28, 2022 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 02, 2016 | The p.Ala141Val variant in ATP6V1B1 has not been previously reported in individu als with hearing loss. This variant has been identified in 2/8650 of East Asian chromosomes and in 8/66542 European chromosomes by the Exome Aggregation Consort ium (ExAC, http://exac.broadinstitute.org; dbSNP rs372842500). Although this va riant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation a nalyses do not provide strong support for or against an impact to the protein. I n summary, the clinical significance of the p.Ala141Val variant is uncertain. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 07, 2022 | The c.422C>T (p.A141V) alteration is located in exon 5 (coding exon 5) of the ATP6V1B1 gene. This alteration results from a C to T substitution at nucleotide position 422, causing the alanine (A) at amino acid position 141 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at