Variant rs2070593 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.04

Variant links:

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]

GPX3 links:

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ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.*249G>A		3_prime_UTR_variant	5/5	ENST00000388825.9
GPX3	NM_001329790.2 linkuse as main transcript	c.*249G>A		3_prime_UTR_variant	6/6

Ensembl

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

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30816

AN:

151964

Hom.:

3725

Cov.:

show subpopulations

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.:

AF XY:

0.246

AC XY:

46657

AN XY:

189886

show subpopulations

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.:

AF XY:

0.207

AC XY:

15421

AN XY:

74320

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over