chr8-10322686-A-G

Variant names:

• chr8-10322686-A-G
• rs4509385
• NM_012331.5:c.543+2697A>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.543+2697A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 152,058 control chromosomes in the GnomAD database, including 24,158 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 0.56 (24158 hom., cov: 32)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.18

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSRA	NM_012331.5	c.543+2697A>G		intron_variant	Intron 5 of 5	ENST00000317173.9	NP_036463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSRA	ENST00000317173.9	c.543+2697A>G		intron_variant	Intron 5 of 5	1	NM_012331.5	ENSP00000313921.4

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84995 AN: 151940 Hom.: 24136 Cov.: 32

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.559 AC: 85059 AN: 152058 Hom.: 24158 Cov.: 32 AF XY: 0.556 AC XY: 41337 AN XY: 74318

African (AFR) AF: 0.612 AC: 25354 AN: 41458

American (AMR) AF: 0.458 AC: 7011 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1739 AN: 3470

East Asian (EAS) AF: 0.392 AC: 2026 AN: 5168

South Asian (SAS) AF: 0.480 AC: 2320 AN: 4832

European-Finnish (FIN) AF: 0.588 AC: 6218 AN: 10568

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.568 AC: 38576 AN: 67948

Other (OTH) AF: 0.534 AC: 1131 AN: 2116

Alfa AF: 0.489 Hom.: 1808

Bravo AF: 0.547

Asia WGS AF: 0.462 AC: 1608 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.9
DANN	Benign	0.62
PhyloP100		2.2
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

Publications

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Other links and lift over

dbSNP: rs4509385; hg19: chr8-10180196;