chr12-65308634-C-T
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Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_001031679.3(MSRB3):c.55C>T(p.Arg19Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,954 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 Pathogenic (no stars).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
MSRB3
NM_001031679.3 stop_gained
NM_001031679.3 stop_gained
Scores
1
4
2
Clinical Significance
Conservation
PhyloP100: 3.05
Genes affected
MSRB3 (HGNC:27375): (methionine sulfoxide reductase B3) The protein encoded by this gene catalyzes the reduction of methionine sulfoxide to methionine. This enzyme acts as a monomer and requires zinc as a cofactor. Several transcript variants encoding two different isoforms have been found for this gene. One of the isoforms localizes to mitochondria while the other localizes to endoplasmic reticula. [provided by RefSeq, Jul 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.901 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 12-65308634-C-T is Pathogenic according to our data. Variant chr12-65308634-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 31056.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr12-65308634-C-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MSRB3 | NM_001031679.3 | c.55C>T | p.Arg19Ter | stop_gained | 2/7 | ENST00000308259.10 | NP_001026849.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MSRB3 | ENST00000308259.10 | c.55C>T | p.Arg19Ter | stop_gained | 2/7 | 1 | NM_001031679.3 | ENSP00000312274 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152186Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 250970Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135626
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GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461650Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727146
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152304Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74478
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 74 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 07, 2011 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A;D;D
Vest4
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: 21
Find out detailed SpliceAI scores and Pangolin per-transcript scores at