chr8-10269174-G-C

Variant names:

• chr8-10269174-G-C
• rs2952182
• NM_012331.5:c.331+23951G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MSRA	NM_012331.5	c.331+23951G>C		intron_variant	Intron 3 of 5	ENST00000317173.9	NP_036463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSRA	ENST00000317173.9	c.331+23951G>C		intron_variant	Intron 3 of 5	1	NM_012331.5	ENSP00000313921.4

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

African (AFR) AF: 0.0625 AC: 2598 AN: 41536

American (AMR) AF: 0.199 AC: 3043 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0683 AC: 237 AN: 3468

East Asian (EAS) AF: 0.106 AC: 547 AN: 5184

South Asian (SAS) AF: 0.0849 AC: 410 AN: 4830

European-Finnish (FIN) AF: 0.0937 AC: 994 AN: 10608

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0590 AC: 4011 AN: 68034

Other (OTH) AF: 0.0756 AC: 160 AN: 2116

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
PhyloP100		2.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2952182; hg19: chr8-10126684;