8-10174238-C-T

Variant names:

• chr8-10174238-C-T
• rs6601419
• NM_012331.5:c.143-33595C>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.143-33595C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,824 control chromosomes in the GnomAD database, including 9,182 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 0.34 (9182 hom., cov: 31)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.850
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 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.143-33595C>T		intron	N/A	NP_036463.1	Q9UJ68-1
	MSRA	NM_001135670.3		c.143-33595C>T		intron	N/A	NP_001129142.1	Q9UJ68-4
	MSRA	NM_001135671.3		c.14-33595C>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.143-33595C>T		intron	N/A	ENSP00000313921.4	Q9UJ68-1
	MSRA	ENST00000382490.9	TSL:1	c.14-33595C>T		intron	N/A	ENSP00000371930.5	Q9UJ68-3
	MSRA	ENST00000528246.5	TSL:1	c.-56-33595C>T		intron	N/A	ENSP00000436839.1	Q9UJ68-2

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52216 AN: 151706 Hom.: 9169 Cov.: 31

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.344 AC: 52259 AN: 151824 Hom.: 9182 Cov.: 31 AF XY: 0.344 AC XY: 25520 AN XY: 74206

African (AFR) AF: 0.302 AC: 12497 AN: 41376

American (AMR) AF: 0.353 AC: 5383 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1265 AN: 3468

East Asian (EAS) AF: 0.467 AC: 2391 AN: 5124

South Asian (SAS) AF: 0.402 AC: 1931 AN: 4798

European-Finnish (FIN) AF: 0.330 AC: 3488 AN: 10558

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.355 AC: 24123 AN: 67926

Other (OTH) AF: 0.351 AC: 739 AN: 2104

Alfa AF: 0.207 Hom.: 430

Bravo AF: 0.350

Asia WGS AF: 0.447 AC: 1554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.30
DANN	Benign	0.36
PhyloP100		-0.85
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: rs6601419; hg19: chr8-10031748;