rs6601414

Variant names:

• chr8-10119238-G-A
• rs6601414
• NM_012331.5:c.142+64580G>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.142+64580G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 152,092 control chromosomes in the GnomAD database, including 19,729 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 (19729 hom., cov: 33)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320
• Publications: 9 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]

ENSG00000285675 (HGNC:):

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 = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSRA	NM_012331.5	c.142+64580G>A		intron_variant	Intron 1 of 5	ENST00000317173.9	NP_036463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSRA	ENST00000317173.9	c.142+64580G>A		intron_variant	Intron 1 of 5	1	NM_012331.5	ENSP00000313921.4

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75290 AN: 151974 Hom.: 19692 Cov.: 33

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.947

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.496 AC: 75377 AN: 152092 Hom.: 19729 Cov.: 33 AF XY: 0.509 AC XY: 37864 AN XY: 74342

African (AFR) AF: 0.433 AC: 17955 AN: 41492

American (AMR) AF: 0.618 AC: 9447 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1334 AN: 3470

East Asian (EAS) AF: 0.947 AC: 4908 AN: 5182

South Asian (SAS) AF: 0.611 AC: 2947 AN: 4824

European-Finnish (FIN) AF: 0.600 AC: 6346 AN: 10570

Middle Eastern (MID) AF: 0.401 AC: 117 AN: 292

European-Non Finnish (NFE) AF: 0.452 AC: 30708 AN: 67954

Other (OTH) AF: 0.480 AC: 1013 AN: 2112

Alfa AF: 0.453 Hom.: 2638

Bravo AF: 0.500

Asia WGS AF: 0.736 AC: 2557 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	0.20
DANN	Benign	0.73
PhyloP100		-0.32
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: rs6601414; hg19: chr8-9976748; COSMIC: COSV57803661;