rs877390

Variant names:

• chr8-10167303-G-A
• rs877390
• NM_012331.5:c.143-40530G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-10167303-G-A
• chr8-10167303-G-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.143-40530G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0564 in 152,208 control chromosomes in the GnomAD database, including 414 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 0.056 (414 hom., cov: 32)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSRA	NM_012331.5	c.143-40530G>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.143-40530G>A		intron_variant	Intron 1 of 5	1	NM_012331.5	ENSP00000313921.4

Frequencies

GnomAD3 genomes AF: 0.0563 AC: 8561 AN: 152090 Hom.: 415 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0272

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0185

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0302

Gnomad OTH AF: 0.0431

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

GnomAD4 genome AF: 0.0564 AC: 8579 AN: 152208 Hom.: 414 Cov.: 32 AF XY: 0.0561 AC XY: 4175 AN XY: 74420

African (AFR) AF: 0.125 AC: 5182 AN: 41512

American (AMR) AF: 0.0271 AC: 415 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 48 AN: 3472

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5178

South Asian (SAS) AF: 0.118 AC: 571 AN: 4828

European-Finnish (FIN) AF: 0.0185 AC: 196 AN: 10594

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0302 AC: 2054 AN: 68014

Other (OTH) AF: 0.0427 AC: 90 AN: 2110

Alfa AF: 0.0246 Hom.: 24

Bravo AF: 0.0559

Asia WGS AF: 0.0730 AC: 252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.53
DANN	Benign	0.54
PhyloP100		-0.14
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: rs877390; hg19: chr8-10024813;