rs2070593

chr5-151028379-G-Achr5-151028379-G-Cchr5-151028379-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
GPX3	NM_002084.5	c.*249G>A		3_prime_UTR_variant	5/5	ENST00000388825.9
GPX3	NM_001329790.2	c.*249G>A		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPX3	ENST00000388825.9	c.*249G>A		3_prime_UTR_variant	5/5	1	NM_002084.5	P1
GPX3	ENST00000521632.1	c.*215G>A		3_prime_UTR_variant	3/3	5

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

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.248

Gnomad4 ASJ exome AF: 0.244

Gnomad4 EAS exome AF: 0.559

Gnomad4 SAS exome AF: 0.329

Gnomad4 FIN exome AF: 0.218

Gnomad4 NFE exome AF: 0.190

Gnomad4 OTH exome AF: 0.232

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

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.600

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.218

Alfa AF: 0.188 Hom.: 2411

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2070593; hg19: chr5-150407940;