rs12679328

chr8-10060873-A-Gchr8-10060873-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_012331.5(MSRA):c.142+6215A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 152,026 control chromosomes in the GnomAD database, including 22,049 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 0.52 (22049 hom., cov: 32)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

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]

LOC124901885 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSRA	NM_012331.5	c.142+6215A>G		intron_variant		ENST00000317173.9
LOC124901885	XR_007060815.1	n.3031A>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSRA	ENST00000317173.9	c.142+6215A>G		intron_variant		1	NM_012331.5	P1
MSRA	ENST00000441698.6	c.142+6215A>G		intron_variant		2
MSRA	ENST00000518255.5	c.142+6215A>G		intron_variant		5
MSRA	ENST00000521209.6	c.-57+1774A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78419 AN: 151908 Hom.: 22065 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.789

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.562

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

GnomAD4 genome AF: 0.516 AC: 78389 AN: 152026 Hom.: 22049 Cov.: 32 AF XY: 0.517 AC XY: 38448 AN XY: 74312

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.679

Gnomad4 EAS AF: 0.544

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.656

Gnomad4 NFE AF: 0.625

Gnomad4 OTH AF: 0.553

Alfa AF: 0.415 Hom.: 1212

Bravo AF: 0.498

Asia WGS AF: 0.461 AC: 1603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
Cadd	Benign	16
Dann	Benign	0.70

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: rs12679328; hg19: chr8-9918383;