rs387907088
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate
The NM_001031679.3(MSRB3):āc.244T>Gā(p.Cys82Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000137 in 1,459,706 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 (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.000014 ( 0 hom. )
Consequence
MSRB3
NM_001031679.3 missense
NM_001031679.3 missense
Scores
14
3
2
Clinical Significance
Conservation
PhyloP100: 6.79
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 8 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.953
PP5
?
Variant 12-65328584-T-G is Pathogenic according to our data. Variant chr12-65328584-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 31055.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-65328584-T-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MSRB3 | NM_001031679.3 | c.244T>G | p.Cys82Gly | missense_variant | 4/7 | ENST00000308259.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MSRB3 | ENST00000308259.10 | c.244T>G | p.Cys82Gly | missense_variant | 4/7 | 1 | NM_001031679.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251248Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135816
GnomAD3 exomes
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1459706Hom.: 0 Cov.: 29 AF XY: 0.0000248 AC XY: 18AN XY: 726380
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ExAC
?
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3
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 74 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Neuberg Centre For Genomic Medicine, NCGM | - | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 07, 2011 | - - |
Hearing loss, autosomal recessive Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | University of Washington Center for Mendelian Genomics, University of Washington | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Benign
DEOGEN2
Pathogenic
D;.;D;.;.;.;D;.;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;.;D;.;D;.;D;D;.;.;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;.;.;.;.;.;.;.;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D;D;D;.;D;.;.;.;.
REVEL
Pathogenic
Sift
Pathogenic
D;D;D;D;D;.;D;.;.;.;.
Sift4G
Pathogenic
D;D;D;D;D;.;D;D;.;.;.
Polyphen
D;D;.;D;.;D;.;D;D;D;.
Vest4
MutPred
Gain of catalytic residue at K85 (P = 0);.;Gain of catalytic residue at K85 (P = 0);.;.;.;.;.;.;.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at