8-10174238-C-T

Variant summary

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

The NM_012331.5(MSRA):c.143-33595C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,824 control chromosomes in the GnomAD database, including 9,182 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 0.34 (9182 hom., cov: 31)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.850

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSRA	NM_012331.5	c.143-33595C>T		intron_variant		ENST00000317173.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSRA	ENST00000317173.9	c.143-33595C>T		intron_variant		1	NM_012331.5	P1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52216 AN: 151706 Hom.: 9169 Cov.: 31

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.344 AC: 52259 AN: 151824 Hom.: 9182 Cov.: 31 AF XY: 0.344 AC XY: 25520 AN XY: 74206

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.402

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.351

Alfa AF: 0.207 Hom.: 430

Bravo AF: 0.350

Asia WGS AF: 0.447 AC: 1554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.30
Dann	Benign	0.36

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: rs6601419; hg19: chr8-10031748;