rs1976274

chr12-65393318-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001031679.3(MSRB3):c.292+24292G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 151,950 control chromosomes in the GnomAD database, including 26,882 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.59 (26882 hom., cov: 32)
• Consequence: MSRB3 NM_001031679.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.883

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSRB3	NM_001031679.3	c.292+24292G>A		intron_variant		ENST00000308259.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSRB3	ENST00000308259.10	c.292+24292G>A		intron_variant		1	NM_001031679.3	P1

Frequencies

GnomAD3 genomes AF: 0.586 AC: 88908 AN: 151832 Hom.: 26869 Cov.: 32

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.699

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.598

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.585 AC: 88958 AN: 151950 Hom.: 26882 Cov.: 32 AF XY: 0.591 AC XY: 43865 AN XY: 74278

Gnomad4 AFR AF: 0.428

Gnomad4 AMR AF: 0.701

Gnomad4 ASJ AF: 0.599

Gnomad4 EAS AF: 0.567

Gnomad4 SAS AF: 0.713

Gnomad4 FIN AF: 0.713

Gnomad4 NFE AF: 0.626

Gnomad4 OTH AF: 0.591

Alfa AF: 0.603 Hom.: 3540

Bravo AF: 0.578

Asia WGS AF: 0.611 AC: 2126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.1
Dann	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1976274; hg19: chr12-65787098; COSMIC: COSV57588696;