8-10343414-G-T

Variant names:

• chr8-10343414-G-T
• rs4841322
• NM_012331.5:c.543+23425G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000317173.9(MSRA):​c.543+23425G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.84 in 152,210 control chromosomes in the GnomAD database, including 54,413 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 0.84 (54413 hom., cov: 33)
• Consequence: MSRA ENST00000317173.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.653
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• 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: ENST00000317173.9. 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+23425G>T		intron	N/A	NP_036463.1
	MSRA	NM_001135670.3		c.423+23425G>T		intron	N/A	NP_001129142.1
	MSRA	NM_001135671.3		c.414+23425G>T		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+23425G>T		intron	N/A	ENSP00000313921.4
	MSRA	ENST00000382490.9	TSL:1	c.414+23425G>T		intron	N/A	ENSP00000371930.5
	MSRA	ENST00000528246.5	TSL:1	c.345+23425G>T		intron	N/A	ENSP00000436839.1

Frequencies

GnomAD3 genomes AF: 0.840 AC: 127812 AN: 152092 Hom.: 54378 Cov.: 33

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.881

Gnomad AMR AF: 0.889

Gnomad ASJ AF: 0.909

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.933

Gnomad FIN AF: 0.904

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.904

Gnomad OTH AF: 0.867

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

GnomAD4 genome AF: 0.840 AC: 127899 AN: 152210 Hom.: 54413 Cov.: 33 AF XY: 0.841 AC XY: 62559 AN XY: 74406

African (AFR) AF: 0.702 AC: 29122 AN: 41486

American (AMR) AF: 0.889 AC: 13610 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.909 AC: 3155 AN: 3472

East Asian (EAS) AF: 0.682 AC: 3527 AN: 5172

South Asian (SAS) AF: 0.933 AC: 4503 AN: 4824

European-Finnish (FIN) AF: 0.904 AC: 9582 AN: 10602

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.904 AC: 61507 AN: 68034

Other (OTH) AF: 0.868 AC: 1836 AN: 2114

Alfa AF: 0.870 Hom.: 12815

Bravo AF: 0.832

Asia WGS AF: 0.817 AC: 2840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	13
DANN	Benign	0.74
PhyloP100		0.65
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: rs4841322; hg19: chr8-10200924; COSMIC: COSV57805380;