8-10155051-T-G

Variant names:

• chr8-10155051-T-G
• rs10090541
• NM_012331.5:c.143-52782T>G

Variant summary

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

The NM_012331.5(MSRA):​c.143-52782T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 139,856 control chromosomes in the GnomAD database, including 3,910 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 (3910 hom., cov: 30)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35

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]

LOC124901886 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSRA	NM_012331.5	c.143-52782T>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.143-52782T>G		intron_variant	Intron 1 of 5	1	NM_012331.5	ENSP00000313921.4

Frequencies

GnomAD3 genomes AF: 0.206 AC: 28846 AN: 139780 Hom.: 3912 Cov.: 30

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.0667

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.107

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.206 AC: 28861 AN: 139856 Hom.: 3910 Cov.: 30 AF XY: 0.212 AC XY: 14355 AN XY: 67782

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.0667

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.169

Alfa AF: 0.0729 Hom.: 128

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.5
DANN	Benign	0.68

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: rs10090541; hg19: chr8-10012561;