8-10292057-A-G

Variant names:

• chr8-10292057-A-G
• rs10903323
• NM_012331.5:c.332-9477A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012331.5(MSRA):​c.332-9477A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,166 control chromosomes in the GnomAD database, including 3,110 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 0.16 (3110 hom., cov: 32)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.928
• Publications: 19 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.594 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.332-9477A>G		intron	N/A	NP_036463.1
	MSRA	NM_001135670.3		c.212-9477A>G		intron	N/A	NP_001129142.1
	MSRA	NM_001135671.3		c.203-9477A>G		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.332-9477A>G		intron	N/A	ENSP00000313921.4
	MSRA	ENST00000382490.9	TSL:1	c.203-9477A>G		intron	N/A	ENSP00000371930.5
	MSRA	ENST00000528246.5	TSL:1	c.134-9477A>G		intron	N/A	ENSP00000436839.1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24744 AN: 152048 Hom.: 3102 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.163 AC: 24765 AN: 152166 Hom.: 3110 Cov.: 32 AF XY: 0.174 AC XY: 12938 AN XY: 74384

African (AFR) AF: 0.105 AC: 4374 AN: 41524

American (AMR) AF: 0.308 AC: 4713 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 425 AN: 3470

East Asian (EAS) AF: 0.612 AC: 3157 AN: 5158

South Asian (SAS) AF: 0.358 AC: 1722 AN: 4816

European-Finnish (FIN) AF: 0.177 AC: 1879 AN: 10588

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8007 AN: 68010

Other (OTH) AF: 0.157 AC: 331 AN: 2112

Alfa AF: 0.140 Hom.: 3607

Bravo AF: 0.174

Asia WGS AF: 0.437 AC: 1518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.23
DANN	Benign	0.26
PhyloP100		-0.93
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: rs10903323; hg19: chr8-10149567;