rs12229918

Positions:

• chr12-65368278-G-C
• chr12-65368278-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001031679.3(MSRB3):​c.264-720G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,132 control chromosomes in the GnomAD database, including 6,227 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 0.26 (6227 hom., cov: 32)
• Consequence: MSRB3 NM_001031679.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.27

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSRB3	NM_001031679.3	c.264-720G>C		intron_variant		ENST00000308259.10	NP_001026849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSRB3	ENST00000308259.10	c.264-720G>C		intron_variant		1	NM_001031679.3	ENSP00000312274	P1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39007 AN: 152014 Hom.: 6228 Cov.: 32

Gnomad AFR AF: 0.0680

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.256 AC: 39001 AN: 152132 Hom.: 6227 Cov.: 32 AF XY: 0.255 AC XY: 18966 AN XY: 74384

Gnomad4 AFR AF: 0.0678

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.383

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.360

Gnomad4 OTH AF: 0.288

Alfa AF: 0.188 Hom.: 465

Bravo AF: 0.248

Asia WGS AF: 0.302 AC: 1050 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	20
DANN	Benign	0.67

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: rs12229918; hg19: chr12-65762058;