rs1484642

chr8-10129145-G-C

Variant summary

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

The NM_012331.5(MSRA):c.142+74487G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.91 in 152,216 control chromosomes in the GnomAD database, including 63,207 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 0.91 (63207 hom., cov: 31)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.229

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSRA	NM_012331.5	c.142+74487G>C		intron_variant		ENST00000317173.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSRA	ENST00000317173.9	c.142+74487G>C		intron_variant		1	NM_012331.5	P1
	ENST00000649481.2	n.515-9559C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.910 AC: 138466 AN: 152098 Hom.: 63158 Cov.: 31

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.969

Gnomad AMR AF: 0.947

Gnomad ASJ AF: 0.960

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.895

Gnomad FIN AF: 0.910

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.928

Gnomad OTH AF: 0.930

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

GnomAD4 genome AF: 0.910 AC: 138574 AN: 152216 Hom.: 63207 Cov.: 31 AF XY: 0.910 AC XY: 67691 AN XY: 74398

Gnomad4 AFR AF: 0.856

Gnomad4 AMR AF: 0.947

Gnomad4 ASJ AF: 0.960

Gnomad4 EAS AF: 0.965

Gnomad4 SAS AF: 0.896

Gnomad4 FIN AF: 0.910

Gnomad4 NFE AF: 0.928

Gnomad4 OTH AF: 0.930

Alfa AF: 0.925 Hom.: 36102

Bravo AF: 0.914

Asia WGS AF: 0.913 AC: 3175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	1.7
Dann	Benign	0.42

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: rs1484642; hg19: chr8-9986655;