NM_012331.5:c.142+46153A>C

Variant names:

• chr8-10100811-A-C
• rs4840463
• NM_012331.5:c.142+46153A>C

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+46153A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 151,852 control chromosomes in the GnomAD database, including 29,104 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 0.60 (29104 hom., cov: 31)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.507
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.696 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+46153A>C		intron	N/A	NP_036463.1
	MSRA	NM_001135670.3		c.142+46153A>C		intron	N/A	NP_001129142.1
	MSRA	NM_001135671.3		c.13+4768A>C		intron	N/A	NP_001129143.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSRA	ENST00000317173.9	TSL:1 MANE Select	c.142+46153A>C		intron	N/A	ENSP00000313921.4
	MSRA	ENST00000382490.9	TSL:1	c.13+4768A>C		intron	N/A	ENSP00000371930.5
	MSRA	ENST00000528246.5	TSL:1	c.-57+4493A>C		intron	N/A	ENSP00000436839.1

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91589 AN: 151734 Hom.: 29120 Cov.: 31

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.804

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.765

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.726

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.655

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

GnomAD4 genome AF: 0.603 AC: 91579 AN: 151852 Hom.: 29104 Cov.: 31 AF XY: 0.603 AC XY: 44710 AN XY: 74190

African (AFR) AF: 0.394 AC: 16312 AN: 41398

American (AMR) AF: 0.630 AC: 9614 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.765 AC: 2653 AN: 3466

East Asian (EAS) AF: 0.579 AC: 2982 AN: 5152

South Asian (SAS) AF: 0.589 AC: 2829 AN: 4806

European-Finnish (FIN) AF: 0.689 AC: 7250 AN: 10526

Middle Eastern (MID) AF: 0.723 AC: 211 AN: 292

European-Non Finnish (NFE) AF: 0.701 AC: 47634 AN: 67936

Other (OTH) AF: 0.646 AC: 1361 AN: 2108

Alfa AF: 0.631 Hom.: 26153

Bravo AF: 0.590

Asia WGS AF: 0.533 AC: 1853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.43
DANN	Benign	0.70
PhyloP100		-0.51
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: rs4840463; hg19: chr8-9958321;