8-10251393-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+6170G>C variant causes a intron change. The variant allele was found at a frequency of 0.209 in 151,924 control chromosomes in the GnomAD database, including 3,434 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 0.21 (3434 hom., cov: 32)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.83

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=-0.35).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSRA	NM_012331.5	c.331+6170G>C		intron_variant		ENST00000317173.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSRA	ENST00000317173.9	c.331+6170G>C		intron_variant		1	NM_012331.5	P1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31789 AN: 151806 Hom.: 3432 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.209 AC: 31809 AN: 151924 Hom.: 3434 Cov.: 32 AF XY: 0.215 AC XY: 15995 AN XY: 74224

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.356

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.174

Alfa AF: 0.0926 Hom.: 139

Bravo AF: 0.205

Asia WGS AF: 0.341 AC: 1184 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	12
Dann	Benign	0.71

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: rs10503405; hg19: chr8-10108903;