chr7-138798119-C-T
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_001085429.2(TMEM213):c.15C>T(p.Pro5=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000206 in 1,599,864 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000019 ( 0 hom. )
Consequence
TMEM213
NM_001085429.2 synonymous
NM_001085429.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.999
Genes affected
TMEM213 (HGNC:27220): (transmembrane protein 213) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]
ATP6V0A4 (HGNC:866): (ATPase H+ transporting V0 subunit a4) This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of intracellular compartments of eukaryotic cells. V-ATPase dependent 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. This gene is one of four genes in man and mouse that encode different isoforms of the a subunit. Alternatively spliced transcript variants encoding the same protein have been described. Mutations in this gene are associated with renal tubular acidosis associated with preserved hearing. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP7
Synonymous conserved (PhyloP=0.999 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| TMEM213 | NM_001085429.2 | c.15C>T | p.Pro5= | synonymous_variant | 1/3 | ENST00000442682.7 | |
| ATP6V0A4 | NM_020632.3 | c.-206G>A | 5_prime_UTR_variant | 1/22 | ENST00000310018.7 | ||
| ATP6V0A4 | NM_130840.3 | c.-103G>A | 5_prime_UTR_variant | 1/21 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TMEM213 | ENST00000442682.7 | c.15C>T | p.Pro5= | synonymous_variant | 1/3 | 1 | NM_001085429.2 | P4 | |
| ATP6V0A4 | ENST00000310018.7 | c.-206G>A | 5_prime_UTR_variant | 1/22 | 1 | NM_020632.3 | P1 |
Frequencies
GnomAD3 genomes 0.0000329 AC: 5AN: 152166Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.00000893 AC: 2AN: 223998Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 121450
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GnomAD4 exome AF: 0.0000193 AC: 28AN: 1447698Hom.: 0 Cov.: 31 AF XY: 0.0000209 AC XY: 15AN XY: 718682
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GnomAD4 genome 0.0000329 AC: 5AN: 152166Hom.: 0 Cov.: 30 AF XY: 0.0000134 AC XY: 1AN XY: 74350
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal recessive distal renal tubular acidosis Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
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