NM_012331.5:c.142+69937C>T

Variant names:

• chr8-10124595-C-T
• rs17151140
• NM_012331.5:c.142+69937C>T

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+69937C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,064 control chromosomes in the GnomAD database, including 4,533 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 0.24 (4533 hom., cov: 33)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36
• Publications: 3 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]

ENSG00000285675 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSRA	NM_012331.5	c.142+69937C>T		intron_variant	Intron 1 of 5	ENST00000317173.9	NP_036463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSRA	ENST00000317173.9	c.142+69937C>T		intron_variant	Intron 1 of 5	1	NM_012331.5	ENSP00000313921.4

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36009 AN: 151946 Hom.: 4522 Cov.: 33

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.237 AC: 36052 AN: 152064 Hom.: 4533 Cov.: 33 AF XY: 0.240 AC XY: 17831 AN XY: 74336

African (AFR) AF: 0.156 AC: 6493 AN: 41506

American (AMR) AF: 0.285 AC: 4351 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 735 AN: 3470

East Asian (EAS) AF: 0.395 AC: 2036 AN: 5156

South Asian (SAS) AF: 0.313 AC: 1508 AN: 4816

European-Finnish (FIN) AF: 0.286 AC: 3015 AN: 10550

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17176 AN: 67968

Other (OTH) AF: 0.250 AC: 528 AN: 2112

Alfa AF: 0.242 Hom.: 1528

Bravo AF: 0.236

Asia WGS AF: 0.361 AC: 1259 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	18
DANN	Benign	0.63
PhyloP100		1.4
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: rs17151140; hg19: chr8-9982105;