rs17765901

chr8-10391970-G-T

Variant summary

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

The NM_012331.5(MSRA):c.544-36178G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 152,036 control chromosomes in the GnomAD database, including 12,914 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 (12914 hom., cov: 32)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.362

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 (NFE) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSRA	NM_012331.5	c.544-36178G>T		intron_variant		ENST00000317173.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSRA	ENST00000317173.9	c.544-36178G>T		intron_variant		1	NM_012331.5	P1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59822 AN: 151916 Hom.: 12911 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.0409

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.394 AC: 59834 AN: 152036 Hom.: 12914 Cov.: 32 AF XY: 0.384 AC XY: 28505 AN XY: 74302

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.0408

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.410

Alfa AF: 0.476 Hom.: 35205

Bravo AF: 0.378

Asia WGS AF: 0.224 AC: 779 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	0.43
Dann	Benign	0.67

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: rs17765901; hg19: chr8-10249480;