8-10083511-C-T

Variant names:

• chr8-10083511-C-T
• rs814422
• NM_012331.5:c.142+28853C>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.142+28853C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,010 control chromosomes in the GnomAD database, including 3,696 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 0.21 (3696 hom., cov: 33)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.24
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 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.142+28853C>T		intron	N/A	NP_036463.1	Q9UJ68-1
	MSRA	NM_001135670.3		c.142+28853C>T		intron	N/A	NP_001129142.1	Q9UJ68-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSRA	ENST00000317173.9	TSL:1 MANE Select	c.142+28853C>T		intron	N/A	ENSP00000313921.4	Q9UJ68-1
	MSRA	ENST00000897533.1		c.142+28853C>T		intron	N/A	ENSP00000567592.1
	MSRA	ENST00000897536.1		c.142+28853C>T		intron	N/A	ENSP00000567595.1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32589 AN: 151892 Hom.: 3678 Cov.: 33

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.215 AC: 32644 AN: 152010 Hom.: 3696 Cov.: 33 AF XY: 0.216 AC XY: 16071 AN XY: 74294

African (AFR) AF: 0.153 AC: 6362 AN: 41460

American (AMR) AF: 0.274 AC: 4190 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 638 AN: 3470

East Asian (EAS) AF: 0.394 AC: 2031 AN: 5156

South Asian (SAS) AF: 0.246 AC: 1186 AN: 4830

European-Finnish (FIN) AF: 0.230 AC: 2431 AN: 10554

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15156 AN: 67956

Other (OTH) AF: 0.218 AC: 461 AN: 2112

Alfa AF: 0.223 Hom.: 2677

Bravo AF: 0.219

Asia WGS AF: 0.334 AC: 1158 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.017
DANN	Benign	0.58
PhyloP100		-3.2
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: rs814422; hg19: chr8-9941021;