8-10295089-T-C

Variant names:

• chr8-10295089-T-C
• rs4840475
• NM_012331.5:c.332-6445T>C

Variant summary

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

The NM_012331.5(MSRA):​c.332-6445T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 151,964 control chromosomes in the GnomAD database, including 43,132 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 0.75 (43132 hom., cov: 31)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• Publications: 5 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSRA	NM_012331.5	c.332-6445T>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.332-6445T>C		intron_variant	Intron 3 of 5	1	NM_012331.5	ENSP00000313921.4

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113722 AN: 151846 Hom.: 43079 Cov.: 31

Gnomad AFR AF: 0.840

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.891

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.744

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

GnomAD4 genome AF: 0.749 AC: 113829 AN: 151964 Hom.: 43132 Cov.: 31 AF XY: 0.746 AC XY: 55416 AN XY: 74248

African (AFR) AF: 0.840 AC: 34839 AN: 41462

American (AMR) AF: 0.764 AC: 11682 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.768 AC: 2665 AN: 3472

East Asian (EAS) AF: 0.891 AC: 4570 AN: 5128

South Asian (SAS) AF: 0.681 AC: 3272 AN: 4802

European-Finnish (FIN) AF: 0.640 AC: 6747 AN: 10546

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.702 AC: 47688 AN: 67950

Other (OTH) AF: 0.736 AC: 1556 AN: 2114

Alfa AF: 0.723 Hom.: 74159

Bravo AF: 0.766

Asia WGS AF: 0.758 AC: 2636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.24
PhyloP100		-1.8
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: rs4840475; hg19: chr8-10152599;