8-10295572-C-T

Variant names:

• chr8-10295572-C-T
• rs17151637
• NM_012331.5:c.332-5962C>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.332-5962C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,090 control chromosomes in the GnomAD database, including 5,885 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 0.27 (5885 hom., cov: 32)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.361
• Publications: 6 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSRA	NM_012331.5	c.332-5962C>T		intron_variant	Intron 3 of 5	ENST00000317173.9	NP_036463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSRA	ENST00000317173.9	c.332-5962C>T		intron_variant	Intron 3 of 5	1	NM_012331.5	ENSP00000313921.4

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40878 AN: 151972 Hom.: 5887 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.00425

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.269 AC: 40879 AN: 152090 Hom.: 5885 Cov.: 32 AF XY: 0.263 AC XY: 19581 AN XY: 74334

African (AFR) AF: 0.327 AC: 13565 AN: 41488

American (AMR) AF: 0.170 AC: 2593 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 898 AN: 3470

East Asian (EAS) AF: 0.00426 AC: 22 AN: 5170

South Asian (SAS) AF: 0.232 AC: 1119 AN: 4820

European-Finnish (FIN) AF: 0.255 AC: 2692 AN: 10574

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19150 AN: 67968

Other (OTH) AF: 0.243 AC: 512 AN: 2110

Alfa AF: 0.264 Hom.: 9260

Bravo AF: 0.260

Asia WGS AF: 0.148 AC: 517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.5
DANN	Benign	0.83
PhyloP100		0.36
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: rs17151637; hg19: chr8-10153082;