8-10138005-A-G

Position:

• chr8-10138005-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000317173.9(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 ENST00000317173.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSRA	NM_012331.5	c.143-69828A>G		intron_variant		ENST00000317173.9	NP_036463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSRA	ENST00000317173.9	c.143-69828A>G		intron_variant		1	NM_012331.5	ENSP00000313921	P1
	ENST00000649481.2	n.514+8960T>C		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.0640

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.565

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.357

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.211

Alfa AF: 0.222 Hom.: 5508

Bravo AF: 0.215

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs12547884; hg19: chr8-9995515; COSMIC: COSV57803683;