rs782329243
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_001692.4(ATP6V1B1):āc.1533T>Cā(p.Thr511=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000472 in 1,610,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.000072 ( 0 hom., cov: 31)
Exomes š: 0.000045 ( 0 hom. )
Consequence
ATP6V1B1
NM_001692.4 synonymous
NM_001692.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.64
Genes affected
ATP6V1B1 (HGNC:853): (ATPase H+ transporting V1 subunit B1) This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain. The V1 domain consists of three A and three B subunits, two G subunits plus the C, D, E, F, and H subunits. The V1 domain contains the ATP catalytic site. The V0 domain consists of five different subunits: a, c, c', c'', and d. Additional isoforms of many of the V1 and V0 subunit proteins are encoded by multiple genes or alternatively spliced transcript variants. This encoded protein is one of two V1 domain B subunit isoforms and is found in the kidney. Mutations in this gene cause distal renal tubular acidosis associated with sensorineural deafness. [provided by RefSeq, Jul 2008]
VAX2 (HGNC:12661): (ventral anterior homeobox 2) This gene encodes a homeobox protein and is almost exclusively expressed in the ventral portion of the retina during development. In mouse studies, this gene was found to be required for the correct formation of the optic fissure and other aspects of retinal development. [provided by RefSeq, Sep 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 2-70965112-T-C is Benign according to our data. Variant chr2-70965112-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 505442.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-4.64 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP6V1B1 | NM_001692.4 | c.1533T>C | p.Thr511= | synonymous_variant | 14/14 | ENST00000234396.10 | |
ATP6V1B1 | XM_011532907.3 | c.1653T>C | p.Thr551= | synonymous_variant | 13/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP6V1B1 | ENST00000234396.10 | c.1533T>C | p.Thr511= | synonymous_variant | 14/14 | 1 | NM_001692.4 | P1 | |
ATP6V1B1 | ENST00000412314.5 | c.1482T>C | p.Thr494= | synonymous_variant | 14/14 | 5 | |||
ATP6V1B1 | ENST00000433895.2 | c.465T>C | p.Thr155= | synonymous_variant | 5/5 | 3 | |||
VAX2 | ENST00000432367.6 | c.*1309T>C | 3_prime_UTR_variant, NMD_transcript_variant | 15/15 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152178Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000489 AC: 12AN: 245232Hom.: 0 AF XY: 0.0000672 AC XY: 9AN XY: 133960
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GnomAD4 exome AF: 0.0000446 AC: 65AN: 1458304Hom.: 0 Cov.: 33 AF XY: 0.0000524 AC XY: 38AN XY: 725662
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GnomAD4 genome AF: 0.0000723 AC: 11AN: 152178Hom.: 0 Cov.: 31 AF XY: 0.0000673 AC XY: 5AN XY: 74334
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 23, 2016 | p.Thr511Thr in exon 14 of ATP6V1B1: This variant is not expected to have clinica l significance because it does not alter an amino acid residue and is not locate d within the splice consensus sequence. It has been identified in 7/63224 Europe an chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinsti tute.org; dbSNP rs782329243). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 04, 2024 | - - |
Renal tubular acidosis with progressive nerve deafness Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 17, 2022 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at