8-10201973-C-G

Variant names:

• chr8-10201973-C-G
• rs7845503
• NM_012331.5:c.143-5860C>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.143-5860C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 152,132 control chromosomes in the GnomAD database, including 22,987 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 0.53 (22987 hom., cov: 34)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.435
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSRA	NM_012331.5	MANE Select	c.143-5860C>G		intron	N/A	NP_036463.1	Q9UJ68-1
	MSRA	NM_001135670.3		c.143-5860C>G		intron	N/A	NP_001129142.1	Q9UJ68-4
	MSRA	NM_001135671.3		c.14-5860C>G		intron	N/A	NP_001129143.1	Q9UJ68-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSRA	ENST00000317173.9	TSL:1 MANE Select	c.143-5860C>G		intron	N/A	ENSP00000313921.4	Q9UJ68-1
	MSRA	ENST00000382490.9	TSL:1	c.14-5860C>G		intron	N/A	ENSP00000371930.5	Q9UJ68-3
	MSRA	ENST00000528246.5	TSL:1	c.-56-5860C>G		intron	N/A	ENSP00000436839.1	Q9UJ68-2

Frequencies

GnomAD3 genomes AF: 0.533 AC: 81072 AN: 152014 Hom.: 22931 Cov.: 34

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.534 AC: 81194 AN: 152132 Hom.: 22987 Cov.: 34 AF XY: 0.532 AC XY: 39567 AN XY: 74376

African (AFR) AF: 0.746 AC: 30971 AN: 41502

American (AMR) AF: 0.471 AC: 7199 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1471 AN: 3468

East Asian (EAS) AF: 0.487 AC: 2517 AN: 5166

South Asian (SAS) AF: 0.597 AC: 2883 AN: 4826

European-Finnish (FIN) AF: 0.417 AC: 4414 AN: 10588

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30153 AN: 67972

Other (OTH) AF: 0.488 AC: 1032 AN: 2114

Alfa AF: 0.347 Hom.: 876

Bravo AF: 0.548

Asia WGS AF: 0.579 AC: 2014 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.5
DANN	Benign	0.70
PhyloP100		0.43
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: rs7845503; hg19: chr8-10059483;