chr8-10344022-G-A

Variant names:

• chr8-10344022-G-A
• rs4841324
• NM_012331.5:c.543+24033G>A

Variant summary

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

The NM_012331.5(MSRA):​c.543+24033G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.859 in 152,128 control chromosomes in the GnomAD database, including 56,470 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 0.86 (56470 hom., cov: 31)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.911 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.543+24033G>A		intron	N/A	NP_036463.1
	MSRA	NM_001135670.3		c.423+24033G>A		intron	N/A	NP_001129142.1
	MSRA	NM_001135671.3		c.414+24033G>A		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.543+24033G>A		intron	N/A	ENSP00000313921.4
	MSRA	ENST00000382490.9	TSL:1	c.414+24033G>A		intron	N/A	ENSP00000371930.5
	MSRA	ENST00000528246.5	TSL:1	c.345+24033G>A		intron	N/A	ENSP00000436839.1

Frequencies

GnomAD3 genomes AF: 0.859 AC: 130568 AN: 152010 Hom.: 56436 Cov.: 31

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.882

Gnomad AMR AF: 0.897

Gnomad ASJ AF: 0.919

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.934

Gnomad FIN AF: 0.904

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.905

Gnomad OTH AF: 0.878

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

GnomAD4 genome AF: 0.859 AC: 130657 AN: 152128 Hom.: 56470 Cov.: 31 AF XY: 0.859 AC XY: 63881 AN XY: 74380

African (AFR) AF: 0.764 AC: 31681 AN: 41456

American (AMR) AF: 0.897 AC: 13722 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.919 AC: 3191 AN: 3472

East Asian (EAS) AF: 0.684 AC: 3521 AN: 5146

South Asian (SAS) AF: 0.934 AC: 4494 AN: 4814

European-Finnish (FIN) AF: 0.904 AC: 9593 AN: 10610

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.905 AC: 61532 AN: 68018

Other (OTH) AF: 0.879 AC: 1856 AN: 2112

Alfa AF: 0.889 Hom.: 271252

Bravo AF: 0.852

Asia WGS AF: 0.822 AC: 2858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.039
DANN	Benign	0.37
PhyloP100		-1.9
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: rs4841324; hg19: chr8-10201532;