8-10138005-A-G

Variant names:

• chr8-10138005-A-G
• rs12547884
• NM_012331.5:c.143-69828A>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.143-69828A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,186 control chromosomes in the GnomAD database, including 4,842 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 (4842 hom., cov: 32)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500
• Publications: 7 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]

ENSG00000285675 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.548 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSRA	NM_012331.5	MANE Select	c.143-69828A>G		intron	N/A	NP_036463.1	Q9UJ68-1
	MSRA	NM_001135670.3		c.143-69828A>G		intron	N/A	NP_001129142.1	Q9UJ68-4
	MSRA	NM_001135671.3		c.13+41962A>G		intron	N/A	NP_001129143.1	Q9UJ68-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSRA	ENST00000317173.9	TSL:1 MANE Select	c.143-69828A>G		intron	N/A	ENSP00000313921.4	Q9UJ68-1
	MSRA	ENST00000382490.9	TSL:1	c.13+41962A>G		intron	N/A	ENSP00000371930.5	Q9UJ68-3
	MSRA	ENST00000528246.5	TSL:1	c.-57+41687A>G		intron	N/A	ENSP00000436839.1	Q9UJ68-2

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33186 AN: 152066 Hom.: 4844 Cov.: 32

Gnomad AFR AF: 0.0640

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.218 AC: 33186 AN: 152186 Hom.: 4842 Cov.: 32 AF XY: 0.231 AC XY: 17161 AN XY: 74402

African (AFR) AF: 0.0640 AC: 2658 AN: 41562

American (AMR) AF: 0.347 AC: 5305 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 575 AN: 3470

East Asian (EAS) AF: 0.565 AC: 2916 AN: 5160

South Asian (SAS) AF: 0.307 AC: 1481 AN: 4828

European-Finnish (FIN) AF: 0.357 AC: 3776 AN: 10574

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15616 AN: 67990

Other (OTH) AF: 0.211 AC: 445 AN: 2114

Alfa AF: 0.219 Hom.: 6884

Bravo AF: 0.215

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.59
PhyloP100		0.0050
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: rs12547884; hg19: chr8-9995515; COSMIC: COSV57803683;