chr8-10165428-G-T

Variant names:

• chr8-10165428-G-T
• rs7017212
• NM_012331.5:c.143-42405G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012331.5(MSRA):​c.143-42405G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 151,892 control chromosomes in the GnomAD database, including 8,684 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 0.32 (8684 hom., cov: 32)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400
• Publications: 7 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.494 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSRA	NM_012331.5	MANE Select	c.143-42405G>T		intron	N/A	NP_036463.1	Q9UJ68-1
	MSRA	NM_001135670.3		c.143-42405G>T		intron	N/A	NP_001129142.1	Q9UJ68-4
	MSRA	NM_001135671.3		c.14-42405G>T		intron	N/A	NP_001129143.1	Q9UJ68-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSRA	ENST00000317173.9	TSL:1 MANE Select	c.143-42405G>T		intron	N/A	ENSP00000313921.4	Q9UJ68-1
	MSRA	ENST00000382490.9	TSL:1	c.14-42405G>T		intron	N/A	ENSP00000371930.5	Q9UJ68-3
	MSRA	ENST00000528246.5	TSL:1	c.-56-42405G>T		intron	N/A	ENSP00000436839.1	Q9UJ68-2

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48770 AN: 151774 Hom.: 8652 Cov.: 32

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.322 AC: 48859 AN: 151892 Hom.: 8684 Cov.: 32 AF XY: 0.331 AC XY: 24601 AN XY: 74230

African (AFR) AF: 0.442 AC: 18278 AN: 41374

American (AMR) AF: 0.327 AC: 4999 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 456 AN: 3464

East Asian (EAS) AF: 0.510 AC: 2634 AN: 5164

South Asian (SAS) AF: 0.454 AC: 2182 AN: 4810

European-Finnish (FIN) AF: 0.346 AC: 3645 AN: 10520

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15767 AN: 67970

Other (OTH) AF: 0.285 AC: 603 AN: 2114

Alfa AF: 0.258 Hom.: 12448

Bravo AF: 0.318

Asia WGS AF: 0.455 AC: 1576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.0
DANN	Benign	0.78
PhyloP100		-0.0040
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: rs7017212; hg19: chr8-10022938;