rs2952182

chr8-10269174-G-C

Variant summary

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

The NM_012331.5(MSRA):c.331+23951G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.079 in 152,266 control chromosomes in the GnomAD database, including 737 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 0.079 (737 hom., cov: 33)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.41

Genes affected

MSRA (HGNC:7377): (methionine sulfoxide reductase A) This gene encodes a ubiquitous and highly conserved protein that carries out the enzymatic reduction of methionine sulfoxide to methionine. Human and animal studies have shown the highest levels of expression in kidney and nervous tissue. The protein functions in the repair of oxidatively damaged proteins to restore biological activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSRA	NM_012331.5	c.331+23951G>C		intron_variant		ENST00000317173.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSRA	ENST00000317173.9	c.331+23951G>C		intron_variant		1	NM_012331.5	P1

Frequencies

GnomAD3 genomes AF: 0.0789 AC: 12010 AN: 152148 Hom.: 732 Cov.: 33

Gnomad AFR AF: 0.0625

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0852

Gnomad FIN AF: 0.0937

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0589

Gnomad OTH AF: 0.0759

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

GnomAD4 genome AF: 0.0790 AC: 12031 AN: 152266 Hom.: 737 Cov.: 33 AF XY: 0.0820 AC XY: 6110 AN XY: 74468

Gnomad4 AFR AF: 0.0625

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.0683

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.0849

Gnomad4 FIN AF: 0.0937

Gnomad4 NFE AF: 0.0590

Gnomad4 OTH AF: 0.0756

Alfa AF: 0.0663 Hom.: 68

Bravo AF: 0.0904

Asia WGS AF: 0.0870 AC: 304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
Cadd	Benign	13
Dann	Benign	0.65

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: rs2952182; hg19: chr8-10126684;