rs10098474

Variant names:

• chr8-10054107-C-T
• rs10098474
• ENST00000562143.1:n.148G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000562143.1(MSRA-DT):​n.148G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 156,812 control chromosomes in the GnomAD database, including 35,440 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 0.65 (34115 hom., cov: 33)
  • Exomes 𝑓: 0.75 (1325 hom.)
• Consequence: MSRA-DT ENST00000562143.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.841
• Publications: 12 publications found

Genes affected

MSRA-DT (HGNC:55400): (MSRA divergent transcript)

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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000562143.1. 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.-410C>T		upstream_gene	N/A	NP_036463.1
	MSRA	NM_001135670.3		c.-410C>T		upstream_gene	N/A	NP_001129142.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSRA-DT	ENST00000562143.1	TSL:6	n.148G>A		non_coding_transcript_exon	Exon 1 of 1
	MSRA-DT	ENST00000659604.1		n.116+819G>A		intron	N/A
	MSRA-DT	ENST00000843173.1		n.32+819G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99529 AN: 152054 Hom.: 34135 Cov.: 33

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.846

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.761

Gnomad OTH AF: 0.701

GnomAD4 exome AF: 0.751 AC: 3485 AN: 4640 Hom.: 1325 Cov.: 0 AF XY: 0.754 AC XY: 1658 AN XY: 2198

African (AFR) AF: 0.408 AC: 62 AN: 152

American (AMR) AF: 0.500 AC: 22 AN: 44

Ashkenazi Jewish (ASJ) AF: 0.820 AC: 100 AN: 122

East Asian (EAS) AF: 0.546 AC: 59 AN: 108

South Asian (SAS) AF: 0.791 AC: 106 AN: 134

European-Finnish (FIN) AF: 0.816 AC: 186 AN: 228

Middle Eastern (MID) AF: 0.625 AC: 10 AN: 16

European-Non Finnish (NFE) AF: 0.771 AC: 2677 AN: 3474

Other (OTH) AF: 0.727 AC: 263 AN: 362

GnomAD4 genome AF: 0.654 AC: 99517 AN: 152172 Hom.: 34115 Cov.: 33 AF XY: 0.655 AC XY: 48710 AN XY: 74388

African (AFR) AF: 0.443 AC: 18374 AN: 41510

American (AMR) AF: 0.622 AC: 9508 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.797 AC: 2767 AN: 3470

East Asian (EAS) AF: 0.598 AC: 3086 AN: 5160

South Asian (SAS) AF: 0.710 AC: 3425 AN: 4824

European-Finnish (FIN) AF: 0.766 AC: 8109 AN: 10584

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.761 AC: 51783 AN: 68012

Other (OTH) AF: 0.692 AC: 1462 AN: 2114

Alfa AF: 0.721 Hom.: 63719

Bravo AF: 0.632

Asia WGS AF: 0.620 AC: 2155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.3
DANN	Benign	0.81
PhyloP100		0.84
PromoterAI		-0.024	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10098474; hg19: chr8-9911617;