rs6601427

Positions:

• chr8-10298515-T-C
• chr8-10298515-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012331.5(MSRA):​c.332-3019T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 151,930 control chromosomes in the GnomAD database, including 22,092 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 0.52 (22092 hom., cov: 31)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSRA	NM_012331.5	c.332-3019T>C		intron_variant		ENST00000317173.9	NP_036463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSRA	ENST00000317173.9	c.332-3019T>C		intron_variant		1	NM_012331.5	ENSP00000313921	P1

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79280 AN: 151810 Hom.: 22062 Cov.: 31

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.00791

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.529

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

GnomAD4 genome AF: 0.522 AC: 79345 AN: 151930 Hom.: 22092 Cov.: 31 AF XY: 0.508 AC XY: 37722 AN XY: 74266

Gnomad4 AFR AF: 0.616

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.00793

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.558

Gnomad4 OTH AF: 0.523

Alfa AF: 0.516 Hom.: 8783

Bravo AF: 0.520

Asia WGS AF: 0.239 AC: 832 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	2.3
DANN	Benign	0.32

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

Publications

LitVar

Other links and lift over

dbSNP: rs6601427; hg19: chr8-10156025;