NM_012331.5:c.143-52782T>G

Variant names:

• chr8-10155051-T-G
• rs10090541
• NM_012331.5:c.143-52782T>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_012331.5(MSRA):​c.143-52782T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 139,856 control chromosomes in the GnomAD database, including 3,910 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 0.21 (3910 hom., cov: 30)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35
• Publications: 3 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]

LOC124901886 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BS2: High Homozygotes in GnomAd4 at 3910 AR gene

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.143-52782T>G		intron	N/A	NP_036463.1
	MSRA	NM_001135670.3		c.143-52782T>G		intron	N/A	NP_001129142.1
	MSRA	NM_001135671.3		c.14-52782T>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.143-52782T>G		intron	N/A	ENSP00000313921.4
	MSRA	ENST00000382490.9	TSL:1	c.14-52782T>G		intron	N/A	ENSP00000371930.5
	MSRA	ENST00000528246.5	TSL:1	c.-56-52782T>G		intron	N/A	ENSP00000436839.1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 28846 AN: 139780 Hom.: 3912 Cov.: 30

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.0667

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.107

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.206 AC: 28861 AN: 139856 Hom.: 3910 Cov.: 30 AF XY: 0.212 AC XY: 14355 AN XY: 67782

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.319 AC: 11607 AN: 36376

American (AMR) AF: 0.210 AC: 2959 AN: 14122

Ashkenazi Jewish (ASJ) AF: 0.0667 AC: 224 AN: 3358

East Asian (EAS) AF: 0.438 AC: 1811 AN: 4136

South Asian (SAS) AF: 0.263 AC: 1128 AN: 4288

European-Finnish (FIN) AF: 0.203 AC: 1838 AN: 9050

Middle Eastern (MID) AF: 0.119 AC: 33 AN: 278

European-Non Finnish (NFE) AF: 0.133 AC: 8678 AN: 65416

Other (OTH) AF: 0.169 AC: 334 AN: 1980

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.164 Hom.: 2999

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.5
DANN	Benign	0.68
PhyloP100		1.4
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: rs10090541; hg19: chr8-10012561;