8-10161207-C-G

Position:

• chr8-10161207-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

MSRA (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MSRA	NM_012331.5	c.143-46626C>G		intron_variant		ENST00000317173.9	NP_036463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSRA	ENST00000317173.9	c.143-46626C>G		intron_variant		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

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.0830

Gnomad4 EAS AF: 0.511

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.196

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

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

LitVar

Other links and lift over

dbSNP: rs6986977; hg19: chr8-10018717; COSMIC: COSV57803724;