12-65278778-C-A
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The ENST00000355192.8(MSRB3):c.10C>A(p.Arg4=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000669 in 1,577,340 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0013 ( 6 hom., cov: 32)
Exomes 𝑓: 0.00060 ( 22 hom. )
Consequence
MSRB3
ENST00000355192.8 synonymous
ENST00000355192.8 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.97
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 Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant 12-65278778-C-A is Benign according to our data. Variant chr12-65278778-C-A is described in ClinVar as [Benign]. Clinvar id is 226730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.97 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00132 (201/152268) while in subpopulation EAS AF= 0.0356 (183/5146). AF 95% confidence interval is 0.0314. There are 6 homozygotes in gnomad4. There are 109 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MSRB3 | NM_001031679.3 | c.-139C>A | 5_prime_UTR_variant | 1/7 | ENST00000308259.10 | NP_001026849.1 | ||
MSRB3 | NM_198080.4 | c.10C>A | p.Arg4= | synonymous_variant | 1/6 | NP_932346.1 | ||
MSRB3 | NM_001193460.2 | c.-303C>A | 5_prime_UTR_variant | 1/8 | NP_001180389.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MSRB3 | ENST00000308259.10 | c.-139C>A | 5_prime_UTR_variant | 1/7 | 1 | NM_001031679.3 | ENSP00000312274 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00131 AC: 200AN: 152150Hom.: 6 Cov.: 32
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GnomAD3 exomes AF: 0.00267 AC: 498AN: 186552Hom.: 14 AF XY: 0.00274 AC XY: 275AN XY: 100328
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GnomAD4 exome AF: 0.000599 AC: 854AN: 1425072Hom.: 22 Cov.: 31 AF XY: 0.000578 AC XY: 408AN XY: 705456
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GnomAD4 genome AF: 0.00132 AC: 201AN: 152268Hom.: 6 Cov.: 32 AF XY: 0.00146 AC XY: 109AN XY: 74446
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 25, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 02, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
MSRB3-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 12, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 31, 2014 | p.Arg4Arg in exon 1A of MSRB3: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 6.3% (126/2014) of East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.br oadinstitute.org, dbSNP rs182726780). - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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Splicing
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at