8-10332530-C-T

Variant names:

• chr8-10332530-C-T
• rs7832708
• NM_012331.5:c.543+12541C>T

Variant summary

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

The NM_012331.5(MSRA):​c.543+12541C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 150,518 control chromosomes in the GnomAD database, including 20,201 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 0.50 (20201 hom., cov: 31)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 21 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=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSRA	NM_012331.5	c.543+12541C>T		intron_variant	Intron 5 of 5	ENST00000317173.9	NP_036463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSRA	ENST00000317173.9	c.543+12541C>T		intron_variant	Intron 5 of 5	1	NM_012331.5	ENSP00000313921.4

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75211 AN: 150404 Hom.: 20175 Cov.: 31

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.458

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.500 AC: 75272 AN: 150518 Hom.: 20201 Cov.: 31 AF XY: 0.514 AC XY: 37761 AN XY: 73478

African (AFR) AF: 0.354 AC: 14398 AN: 40726

American (AMR) AF: 0.643 AC: 9760 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1224 AN: 3452

East Asian (EAS) AF: 0.992 AC: 5129 AN: 5170

South Asian (SAS) AF: 0.629 AC: 2984 AN: 4742

European-Finnish (FIN) AF: 0.628 AC: 6475 AN: 10314

Middle Eastern (MID) AF: 0.461 AC: 131 AN: 284

European-Non Finnish (NFE) AF: 0.497 AC: 33621 AN: 67656

Other (OTH) AF: 0.502 AC: 1050 AN: 2090

Alfa AF: 0.496 Hom.: 16505

Bravo AF: 0.495

Asia WGS AF: 0.761 AC: 2644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	5.3
DANN	Benign	0.79
PhyloP100		-1.0
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: rs7832708; hg19: chr8-10190040;