chr8-10060873-A-G

Variant names:

• chr8-10060873-A-G
• rs12679328
• NM_012331.5:c.142+6215A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012331.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSRA	NM_012331.5	MANE Select	c.142+6215A>G		intron	N/A	NP_036463.1
	MSRA	NM_001135670.3		c.142+6215A>G		intron	N/A	NP_001129142.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSRA	ENST00000317173.9	TSL:1 MANE Select	c.142+6215A>G		intron	N/A	ENSP00000313921.4
	MSRA	ENST00000518255.5	TSL:5	c.142+6215A>G		intron	N/A	ENSP00000429461.1
	MSRA	ENST00000441698.6	TSL:2	c.142+6215A>G		intron	N/A	ENSP00000410912.2

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

African (AFR) AF: 0.283 AC: 11716 AN: 41466

American (AMR) AF: 0.511 AC: 7808 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2354 AN: 3466

East Asian (EAS) AF: 0.544 AC: 2815 AN: 5172

South Asian (SAS) AF: 0.471 AC: 2269 AN: 4818

European-Finnish (FIN) AF: 0.656 AC: 6921 AN: 10556

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.625 AC: 42439 AN: 67952

Other (OTH) AF: 0.553 AC: 1168 AN: 2112

Alfa AF: 0.405 Hom.: 1238

Bravo AF: 0.498

Asia WGS AF: 0.461 AC: 1603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	16
DANN	Benign	0.70
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12679328; hg19: chr8-9918383;