chr12-65442727-C-G

Position:

• chr12-65442727-C-G

Variant summary

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

The NM_001031679.3(MSRB3):​c.293-11001C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0322 in 152,118 control chromosomes in the GnomAD database, including 156 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 0.032 (156 hom., cov: 32)
• Consequence: MSRB3 NM_001031679.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.791

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=-0.44).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.069 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSRB3	NM_001031679.3	c.293-11001C>G		intron_variant		ENST00000308259.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSRB3	ENST00000308259.10	c.293-11001C>G		intron_variant		1	NM_001031679.3	P1

Frequencies

GnomAD3 genomes AF: 0.0320 AC: 4871 AN: 152000 Hom.: 152 Cov.: 32

Gnomad AFR AF: 0.0710

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0184

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.0495

Gnomad SAS AF: 0.0339

Gnomad FIN AF: 0.0293

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0113

Gnomad OTH AF: 0.0291

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

GnomAD4 genome AF: 0.0322 AC: 4899 AN: 152118 Hom.: 156 Cov.: 32 AF XY: 0.0327 AC XY: 2429 AN XY: 74380

Gnomad4 AFR AF: 0.0712

Gnomad4 AMR AF: 0.0183

Gnomad4 ASJ AF: 0.0245

Gnomad4 EAS AF: 0.0498

Gnomad4 SAS AF: 0.0340

Gnomad4 FIN AF: 0.0293

Gnomad4 NFE AF: 0.0112

Gnomad4 OTH AF: 0.0354

Alfa AF: 0.0229 Hom.: 14

Bravo AF: 0.0314

Asia WGS AF: 0.0660 AC: 227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10506523; hg19: chr12-65836507;