rs1994224

Positions:

• chr8-10109076-A-G

Variant summary

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

The NM_012331.5(MSRA):​c.142+54418A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,156 control chromosomes in the GnomAD database, including 3,764 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 0.22 (3764 hom., cov: 32)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSRA	NM_012331.5	c.142+54418A>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.142+54418A>G		intron_variant		1	NM_012331.5	ENSP00000313921	P1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32905 AN: 152038 Hom.: 3751 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.217 AC: 32954 AN: 152156 Hom.: 3764 Cov.: 32 AF XY: 0.218 AC XY: 16253 AN XY: 74386

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.224

Alfa AF: 0.227 Hom.: 1284

Bravo AF: 0.220

Asia WGS AF: 0.365 AC: 1270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.37
DANN	Benign	0.31

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: rs1994224; hg19: chr8-9966586;