rs2070593

Variant names:

• chr5-151028379-G-A
• rs2070593
• NM_002084.5:c.*249G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-151028379-G-A
• chr5-151028379-G-C
• chr5-151028379-G-T

Variant summary

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

The NM_002084.5(GPX3):​c.*249G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 512,544 control chromosomes in the GnomAD database, including 15,946 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 0.20 (3728 hom., cov: 32)
  • Exomes 𝑓: 0.24 (12218 hom.)
• Consequence: GPX3 NM_002084.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.04
• Publications: 34 publications found

Genes affected

GPX3 (HGNC:4555): (glutathione peroxidase 3) The protein encoded by this gene belongs to the glutathione peroxidase family, members of which catalyze the reduction of organic hydroperoxides and hydrogen peroxide (H2O2) by glutathione, and thereby protect cells against oxidative damage. Several isozymes of this gene family exist in vertebrates, which vary in cellular location and substrate specificity. This isozyme is secreted, and is abundantly found in plasma. Downregulation of expression of this gene by promoter hypermethylation has been observed in a wide spectrum of human malignancies, including thyroid cancer, hepatocellular carcinoma and chronic myeloid leukemia. This isozyme is also a selenoprotein, containing the rare amino acid selenocysteine (Sec) at its active site. Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPX3	NM_002084.5	c.*249G>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000388825.9	NP_002075.2
GPX3	NM_001329790.2	c.*249G>A		3_prime_UTR_variant	Exon 6 of 6		NP_001316719.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPX3	ENST00000388825.9	c.*249G>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_002084.5	ENSP00000373477.4
GPX3	ENST00000521632.1	c.*215G>A		3_prime_UTR_variant	Exon 3 of 3	5		ENSP00000430743.2
GPX3	ENST00000517973.1	c.*473G>A		downstream_gene_variant		3		ENSP00000429709.1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30816 AN: 151964 Hom.: 3725 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.217

GnomAD4 exome AF: 0.239 AC: 86077 AN: 360460 Hom.: 12218 Cov.: 0 AF XY: 0.246 AC XY: 46657 AN XY: 189886

African (AFR) AF: 0.146 AC: 1551 AN: 10652

American (AMR) AF: 0.248 AC: 3792 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 2727 AN: 11162

East Asian (EAS) AF: 0.559 AC: 13256 AN: 23724

South Asian (SAS) AF: 0.329 AC: 14483 AN: 44086

European-Finnish (FIN) AF: 0.218 AC: 4717 AN: 21618

Middle Eastern (MID) AF: 0.279 AC: 489 AN: 1750

European-Non Finnish (NFE) AF: 0.190 AC: 40247 AN: 211416

Other (OTH) AF: 0.232 AC: 4815 AN: 20756

GnomAD4 genome AF: 0.203 AC: 30825 AN: 152084 Hom.: 3728 Cov.: 32 AF XY: 0.207 AC XY: 15421 AN XY: 74320

African (AFR) AF: 0.140 AC: 5807 AN: 41490

American (AMR) AF: 0.225 AC: 3438 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 816 AN: 3468

East Asian (EAS) AF: 0.600 AC: 3093 AN: 5158

South Asian (SAS) AF: 0.339 AC: 1633 AN: 4820

European-Finnish (FIN) AF: 0.203 AC: 2148 AN: 10582

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12963 AN: 67960

Other (OTH) AF: 0.218 AC: 460 AN: 2114

Alfa AF: 0.188 Hom.: 2856

Bravo AF: 0.204

Asia WGS AF: 0.396 AC: 1378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.064
DANN	Benign	0.63
PhyloP100		-3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2070593; hg19: chr5-150407940;