chr8-10109076-A-G

Variant names:

• chr8-10109076-A-G
• rs1994224
• NM_012331.5:c.142+54418A>G

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+54418A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,156 control chromosomes in the GnomAD database, including 3,764 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 0.22 (3764 hom., cov: 32)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.396 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+54418A>G		intron	N/A	NP_036463.1
	MSRA	NM_001135670.3		c.142+54418A>G		intron	N/A	NP_001129142.1
	MSRA	NM_001135671.3		c.13+13033A>G		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+54418A>G		intron	N/A	ENSP00000313921.4
	MSRA	ENST00000382490.9	TSL:1	c.13+13033A>G		intron	N/A	ENSP00000371930.5
	MSRA	ENST00000528246.5	TSL:1	c.-57+12758A>G		intron	N/A	ENSP00000436839.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32905 AN: 152038 Hom.: 3751 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.217 AC: 32954 AN: 152156 Hom.: 3764 Cov.: 32 AF XY: 0.218 AC XY: 16253 AN XY: 74386

African (AFR) AF: 0.158 AC: 6557 AN: 41518

American (AMR) AF: 0.263 AC: 4021 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 603 AN: 3470

East Asian (EAS) AF: 0.411 AC: 2124 AN: 5170

South Asian (SAS) AF: 0.315 AC: 1521 AN: 4828

European-Finnish (FIN) AF: 0.218 AC: 2307 AN: 10572

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

European-Non Finnish (NFE) AF: 0.223 AC: 15152 AN: 67988

Other (OTH) AF: 0.224 AC: 474 AN: 2112

Alfa AF: 0.216 Hom.: 2392

Bravo AF: 0.220

Asia WGS AF: 0.365 AC: 1270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.37
DANN	Benign	0.31
PhyloP100		-0.27
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: rs1994224; hg19: chr8-9966586;