chr12-65469804-G-A

Position:

• chr12-65469804-G-A

Variant summary

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

The ENST00000541189.5(MSRB3):​c.435+15979G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,006 control chromosomes in the GnomAD database, including 11,002 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 0.37 (11002 hom., cov: 32)
• Consequence: MSRB3 ENST00000541189.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56

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]

MSRB3-AS1 (HGNC:53386): (MSRB3 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSRB3-AS1	NR_120431.1	n.550-2670C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSRB3	ENST00000541189.5	c.435+15979G>A		intron_variant		3		ENSP00000440722.1
MSRB3	ENST00000446731.2	c.264+15979G>A		intron_variant		3		ENSP00000404903.2
MSRB3	ENST00000647481.1	c.195+15979G>A		intron_variant				ENSP00000496162.1
MSRB3-AS1	ENST00000537250.5	n.376-2670C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55919 AN: 151890 Hom.: 10997 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.368 AC: 55936 AN: 152006 Hom.: 11002 Cov.: 32 AF XY: 0.367 AC XY: 27243 AN XY: 74290

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.467

Gnomad4 EAS AF: 0.449

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.392

Alfa AF: 0.291 Hom.: 1005

Bravo AF: 0.356

Asia WGS AF: 0.357 AC: 1239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.062
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10784460; hg19: chr12-65863584;