8-10228901-G-C

Variant names:

• chr8-10228901-G-C
• rs6999631
• NM_012331.5:c.212-16203G>C

Variant summary

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

The NM_012331.5(MSRA):​c.212-16203G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.837 in 152,084 control chromosomes in the GnomAD database, including 55,888 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 0.84 (55888 hom., cov: 31)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.987
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.957 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.212-16203G>C		intron	N/A	NP_036463.1
	MSRA	NM_001135670.3		c.211+21000G>C		intron	N/A	NP_001129142.1
	MSRA	NM_001135671.3		c.83-16203G>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.212-16203G>C		intron	N/A	ENSP00000313921.4
	MSRA	ENST00000382490.9	TSL:1	c.83-16203G>C		intron	N/A	ENSP00000371930.5
	MSRA	ENST00000528246.5	TSL:1	c.14-16203G>C		intron	N/A	ENSP00000436839.1

Frequencies

GnomAD3 genomes AF: 0.838 AC: 127278 AN: 151968 Hom.: 55884 Cov.: 31

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.971

Gnomad AMR AF: 0.913

Gnomad ASJ AF: 0.937

Gnomad EAS AF: 0.934

Gnomad SAS AF: 0.885

Gnomad FIN AF: 0.959

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.964

Gnomad OTH AF: 0.878

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

GnomAD4 genome AF: 0.837 AC: 127327 AN: 152084 Hom.: 55888 Cov.: 31 AF XY: 0.841 AC XY: 62518 AN XY: 74366

African (AFR) AF: 0.539 AC: 22310 AN: 41384

American (AMR) AF: 0.913 AC: 13967 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.937 AC: 3252 AN: 3470

East Asian (EAS) AF: 0.933 AC: 4812 AN: 5156

South Asian (SAS) AF: 0.884 AC: 4253 AN: 4812

European-Finnish (FIN) AF: 0.959 AC: 10183 AN: 10620

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.964 AC: 65547 AN: 68026

Other (OTH) AF: 0.878 AC: 1855 AN: 2112

Alfa AF: 0.874 Hom.: 3630

Bravo AF: 0.822

Asia WGS AF: 0.901 AC: 3133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.17
DANN	Benign	0.26
PhyloP100		-0.99
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: rs6999631; hg19: chr8-10086411;