8-10251393-G-C

Variant names:

• chr8-10251393-G-C
• rs10503405
• NM_012331.5:c.331+6170G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_012331.5(MSRA):​c.331+6170G>C variant causes a intron change. The variant allele was found at a frequency of 0.209 in 151,924 control chromosomes in the GnomAD database, including 3,434 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 0.21 (3434 hom., cov: 32)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.83
• Publications: 3 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012331.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSRA	NM_012331.5	MANE Select	c.331+6170G>C		intron	N/A	NP_036463.1
	MSRA	NM_001135670.3		c.211+43492G>C		intron	N/A	NP_001129142.1
	MSRA	NM_001135671.3		c.202+6170G>C		intron	N/A	NP_001129143.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSRA	ENST00000317173.9	TSL:1 MANE Select	c.331+6170G>C		intron	N/A	ENSP00000313921.4
	MSRA	ENST00000382490.9	TSL:1	c.202+6170G>C		intron	N/A	ENSP00000371930.5
	MSRA	ENST00000528246.5	TSL:1	c.133+6170G>C		intron	N/A	ENSP00000436839.1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31789 AN: 151806 Hom.: 3432 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.209 AC: 31809 AN: 151924 Hom.: 3434 Cov.: 32 AF XY: 0.215 AC XY: 15995 AN XY: 74224

African (AFR) AF: 0.200 AC: 8296 AN: 41404

American (AMR) AF: 0.209 AC: 3186 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 562 AN: 3470

East Asian (EAS) AF: 0.356 AC: 1834 AN: 5150

South Asian (SAS) AF: 0.301 AC: 1452 AN: 4818

European-Finnish (FIN) AF: 0.244 AC: 2566 AN: 10534

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13364 AN: 67966

Other (OTH) AF: 0.174 AC: 368 AN: 2112

Alfa AF: 0.0926 Hom.: 139

Bravo AF: 0.205

Asia WGS AF: 0.341 AC: 1184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	12
DANN	Benign	0.71
PhyloP100		3.8
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: rs10503405; hg19: chr8-10108903;