rs35393316
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The NM_001031679.3(MSRB3):c.486G>A(p.Ala162Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000439 in 1,614,162 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.0023 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00025 ( 0 hom. )
Consequence
MSRB3
NM_001031679.3 synonymous
NM_001031679.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0210
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 -15 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
Variant 12-65463250-G-A is Benign according to our data. Variant chr12-65463250-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 178616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-65463250-G-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-0.021 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00229 (349/152274) while in subpopulation AFR AF= 0.00797 (331/41542). AF 95% confidence interval is 0.00726. There are 0 homozygotes in gnomad4. There are 161 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MSRB3 | NM_001031679.3 | c.486G>A | p.Ala162Ala | synonymous_variant | 7/7 | ENST00000308259.10 | NP_001026849.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MSRB3 | ENST00000308259.10 | c.486G>A | p.Ala162Ala | synonymous_variant | 7/7 | 1 | NM_001031679.3 | ENSP00000312274.6 |
Frequencies
GnomAD3 genomes AF: 0.00229 AC: 349AN: 152156Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000636 AC: 160AN: 251456Hom.: 0 AF XY: 0.000486 AC XY: 66AN XY: 135904
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GnomAD4 exome AF: 0.000246 AC: 359AN: 1461888Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 156AN XY: 727246
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GnomAD4 genome AF: 0.00229 AC: 349AN: 152274Hom.: 0 Cov.: 33 AF XY: 0.00216 AC XY: 161AN XY: 74438
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 07, 2012 | Ala162Ala in Exon 08 of MSRB3: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 0.6% (23/3738) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs35393316). - |
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 20, 2015 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 21, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 10, 2021 | - - |
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