rs4260895

Variant names:

• chr8-10268838-C-A
• rs4260895
• NM_012331.5:c.331+23615C>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+23615C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 152,202 control chromosomes in the GnomAD database, including 43,238 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 (43238 hom., cov: 33)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.258
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSRA	NM_012331.5	c.331+23615C>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+23615C>A		intron_variant	Intron 3 of 5	1	NM_012331.5	ENSP00000313921.4

Frequencies

GnomAD3 genomes AF: 0.752 AC: 114341 AN: 152084 Hom.: 43185 Cov.: 33

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.838

Gnomad ASJ AF: 0.745

Gnomad EAS AF: 0.955

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.732

Gnomad OTH AF: 0.774

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

GnomAD4 genome AF: 0.752 AC: 114458 AN: 152202 Hom.: 43238 Cov.: 33 AF XY: 0.756 AC XY: 56258 AN XY: 74426

African (AFR) AF: 0.725 AC: 30094 AN: 41500

American (AMR) AF: 0.838 AC: 12825 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 2586 AN: 3472

East Asian (EAS) AF: 0.955 AC: 4941 AN: 5174

South Asian (SAS) AF: 0.744 AC: 3587 AN: 4822

European-Finnish (FIN) AF: 0.762 AC: 8087 AN: 10608

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.732 AC: 49797 AN: 68008

Other (OTH) AF: 0.775 AC: 1640 AN: 2116

Alfa AF: 0.742 Hom.: 52112

Bravo AF: 0.759

Asia WGS AF: 0.828 AC: 2879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.29
DANN	Benign	0.19
PhyloP100		-0.26
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: rs4260895; hg19: chr8-10126348;