8-10083511-C-T

Position:

• chr8-10083511-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000317173.9(MSRA):​c.142+28853C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,010 control chromosomes in the GnomAD database, including 3,696 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 0.21 (3696 hom., cov: 33)
• Consequence: MSRA ENST00000317173.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.24

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSRA	NM_012331.5	c.142+28853C>T		intron_variant		ENST00000317173.9	NP_036463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSRA	ENST00000317173.9	c.142+28853C>T		intron_variant		1	NM_012331.5	ENSP00000313921	P1
MSRA	ENST00000441698.6	c.142+28853C>T		intron_variant		2		ENSP00000410912
MSRA	ENST00000518255.5	c.142+28853C>T		intron_variant		5		ENSP00000429461
MSRA	ENST00000521209.6	c.-57+24412C>T		intron_variant		3		ENSP00000435644

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32589 AN: 151892 Hom.: 3678 Cov.: 33

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.215 AC: 32644 AN: 152010 Hom.: 3696 Cov.: 33 AF XY: 0.216 AC XY: 16071 AN XY: 74294

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.218

Alfa AF: 0.220 Hom.: 1775

Bravo AF: 0.219

Asia WGS AF: 0.334 AC: 1158 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.017
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: rs814422; hg19: chr8-9941021;