rs121908367
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The ENST00000310018.7(ATP6V0A4):c.2257C>T(p.Gln753Ter) variant causes a stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,613,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
ENST00000310018.7 stop_gained, splice_region
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATP6V0A4 | NM_020632.3 | c.2257C>T | p.Gln753Ter | stop_gained, splice_region_variant | 20/22 | ENST00000310018.7 | NP_065683.2 | |
ATP6V0A4 | NM_130840.3 | c.2257C>T | p.Gln753Ter | stop_gained, splice_region_variant | 19/21 | NP_570855.2 | ||
ATP6V0A4 | NM_130841.3 | c.2257C>T | p.Gln753Ter | stop_gained, splice_region_variant | 19/21 | NP_570856.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ATP6V0A4 | ENST00000310018.7 | c.2257C>T | p.Gln753Ter | stop_gained, splice_region_variant | 20/22 | 1 | NM_020632.3 | ENSP00000308122 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152210Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251456Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135900
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461212Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 726900
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152210Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74368
ClinVar
Submissions by phenotype
Renal tubular acidosis, distal, 3, with or without sensorineural hearing loss Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 2000 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 27, 2022 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Oct 25, 2022 | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34426522, 31589614, 34157794, 28233610, 33083013, 29627839, 10973252) - |
Autosomal recessive distal renal tubular acidosis Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Centogene AG - the Rare Disease Company | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at