rs6983870

Positions:

• chr8-10253784-G-A
• chr8-10253784-G-T

Variant summary

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

The NM_012331.5(MSRA):​c.331+8561G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 151,914 control chromosomes in the GnomAD database, including 7,782 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 0.30 (7782 hom., cov: 32)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150

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=-0.63).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSRA	NM_012331.5	c.331+8561G>A		intron_variant		ENST00000317173.9	NP_036463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSRA	ENST00000317173.9	c.331+8561G>A		intron_variant		1	NM_012331.5	ENSP00000313921	P1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46299 AN: 151796 Hom.: 7776 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.305 AC: 46330 AN: 151914 Hom.: 7782 Cov.: 32 AF XY: 0.294 AC XY: 21792 AN XY: 74208

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.350

Alfa AF: 0.352 Hom.: 1518

Bravo AF: 0.301

Asia WGS AF: 0.0850 AC: 297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.2
DANN	Benign	0.46

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: rs6983870; hg19: chr8-10111294;