chr8-10161207-C-G

Variant names:

• chr8-10161207-C-G
• rs6986977
• NM_012331.5:c.143-46626C>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.143-46626C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,066 control chromosomes in the GnomAD database, including 5,016 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 0.24 (5016 hom., cov: 32)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• Publications: 4 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=-0.6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSRA	NM_012331.5	c.143-46626C>G		intron_variant	Intron 1 of 5	ENST00000317173.9	NP_036463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSRA	ENST00000317173.9	c.143-46626C>G		intron_variant	Intron 1 of 5	1	NM_012331.5	ENSP00000313921.4

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35801 AN: 151950 Hom.: 5013 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.0830

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.236 AC: 35843 AN: 152066 Hom.: 5016 Cov.: 32 AF XY: 0.245 AC XY: 18176 AN XY: 74322

African (AFR) AF: 0.336 AC: 13940 AN: 41480

American (AMR) AF: 0.232 AC: 3540 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0830 AC: 288 AN: 3468

East Asian (EAS) AF: 0.511 AC: 2636 AN: 5160

South Asian (SAS) AF: 0.319 AC: 1536 AN: 4816

European-Finnish (FIN) AF: 0.263 AC: 2778 AN: 10552

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.153 AC: 10379 AN: 68008

Other (OTH) AF: 0.196 AC: 413 AN: 2108

Alfa AF: 0.192 Hom.: 406

Bravo AF: 0.235

Asia WGS AF: 0.386 AC: 1339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	12
DANN	Benign	0.58
PhyloP100		1.0
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: rs6986977; hg19: chr8-10018717; COSMIC: COSV57803724;