rs145536062
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001692.4(ATP6V1B1):c.943C>T(p.Arg315Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,613,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001692.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP6V1B1 | NM_001692.4 | c.943C>T | p.Arg315Ter | stop_gained | 10/14 | ENST00000234396.10 | |
ATP6V1B1 | XM_011532907.3 | c.1063C>T | p.Arg355Ter | stop_gained | 9/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP6V1B1 | ENST00000234396.10 | c.943C>T | p.Arg315Ter | stop_gained | 10/14 | 1 | NM_001692.4 | P1 | |
ATP6V1B1 | ENST00000412314.5 | c.943C>T | p.Arg315Ter | stop_gained | 10/14 | 5 | |||
VAX2 | ENST00000432367.6 | c.*836+295C>T | intron_variant, NMD_transcript_variant | 5 | |||||
VAX2 | ENST00000646783.1 | c.*831C>T | 3_prime_UTR_variant, NMD_transcript_variant | 11/13 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152108Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251442Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135906
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461860Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4AN XY: 727234
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152108Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74304
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Aug 21, 2018 | The R315X variant in the ATP6V1B1 gene has been reported previously in association with distal renal tubular acidosis, in an affected individual who was heterozygous for the R315X variant and another ATP6V1B1 variant, however parental studies were not performed to determine the phase of these two variants (Palazzo et al., 2017). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R315X variant is observed in 5/277140 (0.002%) alleles in large population cohorts (Lek et al., 2016). We interpret R315X as a likely pathogenic variant. - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 26, 2023 | This premature translational stop signal has been observed in individual(s) with distal renal tubular acidosis (PMID: 28233610). ClinVar contains an entry for this variant (Variation ID: 554499). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. This variant is present in population databases (rs145536062, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Arg315*) 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). - |
Renal tubular acidosis with progressive nerve deafness Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Oct 24, 2017 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at