rs7001821

chr8-10272263-T-Cchr8-10272263-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.331+27040T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,908 control chromosomes in the GnomAD database, including 22,990 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 0.55 (22990 hom., cov: 33)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSRA	NM_012331.5	c.331+27040T>C		intron_variant		ENST00000317173.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSRA	ENST00000317173.9	c.331+27040T>C		intron_variant		1	NM_012331.5	P1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82884 AN: 151790 Hom.: 22971 Cov.: 33

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.576

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

GnomAD4 genome AF: 0.546 AC: 82947 AN: 151908 Hom.: 22990 Cov.: 33 AF XY: 0.541 AC XY: 40203 AN XY: 74256

Gnomad4 AFR AF: 0.451

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.614

Gnomad4 OTH AF: 0.577

Alfa AF: 0.594 Hom.: 54812

Bravo AF: 0.536

Asia WGS AF: 0.447 AC: 1556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.5
Dann	Benign	0.73

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: rs7001821; hg19: chr8-10129773;