chr8-10197418-G-T

Variant names:

• chr8-10197418-G-T
• rs4448276
• NM_012331.5:c.143-10415G>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.143-10415G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 151,946 control chromosomes in the GnomAD database, including 11,627 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 0.39 (11627 hom., cov: 32)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.528
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSRA	NM_012331.5	c.143-10415G>T		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.143-10415G>T		intron_variant	Intron 1 of 5	1	NM_012331.5	ENSP00000313921.4

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58903 AN: 151828 Hom.: 11599 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.388 AC: 58980 AN: 151946 Hom.: 11627 Cov.: 32 AF XY: 0.388 AC XY: 28843 AN XY: 74260

African (AFR) AF: 0.338 AC: 13988 AN: 41440

American (AMR) AF: 0.381 AC: 5816 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1434 AN: 3466

East Asian (EAS) AF: 0.444 AC: 2297 AN: 5168

South Asian (SAS) AF: 0.534 AC: 2570 AN: 4812

European-Finnish (FIN) AF: 0.384 AC: 4054 AN: 10552

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.404 AC: 27475 AN: 67940

Other (OTH) AF: 0.381 AC: 800 AN: 2098

Alfa AF: 0.356 Hom.: 2584

Bravo AF: 0.389

Asia WGS AF: 0.507 AC: 1762 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	0.55
DANN	Benign	0.54
PhyloP100		-0.53
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: rs4448276; hg19: chr8-10054928;