NM_012331.5:c.331+2087C>A

Variant names:

• chr8-10247310-C-A
• rs4288376
• NM_012331.5:c.331+2087C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012331.5(MSRA):​c.331+2087C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 150,508 control chromosomes in the GnomAD database, including 5,272 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 0.26 (5272 hom., cov: 32)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.873
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSRA	NM_012331.5	c.331+2087C>A		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+2087C>A		intron_variant	Intron 3 of 5	1	NM_012331.5	ENSP00000313921.4

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39435 AN: 150388 Hom.: 5269 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.262 AC: 39463 AN: 150508 Hom.: 5272 Cov.: 32 AF XY: 0.266 AC XY: 19580 AN XY: 73530

African (AFR) AF: 0.247 AC: 10197 AN: 41354

American (AMR) AF: 0.354 AC: 5365 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 702 AN: 3432

East Asian (EAS) AF: 0.281 AC: 1450 AN: 5158

South Asian (SAS) AF: 0.307 AC: 1436 AN: 4674

European-Finnish (FIN) AF: 0.293 AC: 3072 AN: 10478

Middle Eastern (MID) AF: 0.262 AC: 74 AN: 282

European-Non Finnish (NFE) AF: 0.243 AC: 16295 AN: 67008

Other (OTH) AF: 0.257 AC: 535 AN: 2082

Alfa AF: 0.247 Hom.: 448

Bravo AF: 0.263

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.71
PhyloP100		-0.87
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: rs4288376; hg19: chr8-10104820;