2-70964442-AC-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The ENST00000234396.10(ATP6V1B1):βc.1155delβ(p.Ile386SerfsTer10) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,612,962 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (β ). Synonymous variant affecting the same amino acid position (i.e. Y383Y) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
ENST00000234396.10 frameshift
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATP6V1B1 | NM_001692.4 | c.1155del | p.Ile386SerfsTer10 | frameshift_variant | 12/14 | ENST00000234396.10 | NP_001683.2 | |
ATP6V1B1 | XM_011532907.3 | c.1275del | p.Ile426SerfsTer10 | frameshift_variant | 11/13 | XP_011531209.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ATP6V1B1 | ENST00000234396.10 | c.1155del | p.Ile386SerfsTer10 | frameshift_variant | 12/14 | 1 | NM_001692.4 | ENSP00000234396 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000662 AC: 1AN: 151114Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251074Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135814
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461848Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727228
GnomAD4 genome AF: 0.00000662 AC: 1AN: 151114Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 73728
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 04, 2023 | This sequence change creates a premature translational stop signal (p.Ile386Serfs*10) in the ATP6V1B1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATP6V1B1 are known to be pathogenic (PMID: 9916796, 18368028). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 953951). This variant is also known as P385: 1-bp del. This premature translational stop signal has been observed in individual(s) with renal tubular acidosis and deafness (PMID: 9916796). This variant is present in population databases (rs782051834, gnomAD 0.0009%). - |
Renal tubular acidosis with progressive nerve deafness Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at