Genetic Variant GPX3:c.460-14T>C (chr5-151027895-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002084.5(GPX3):c.460-14T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.83 in 1,609,620 control chromosomes in the GnomAD database, including 556,179 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 0.79 ( 47735 hom., cov: 31)

Exomes 𝑓: 0.83 ( 508444 hom. )

Consequence

GPX3
NM_002084.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.474

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=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPX3	NM_002084.5 link	c.460-14T>C		intron_variant	Intron 4 of 4	ENST00000388825.9	NP_002075.2	P22352
GPX3	NM_001329790.2 link	c.487-14T>C		intron_variant	Intron 5 of 5		NP_001316719.1	P22352

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GPX3	ENST00000388825.9 link	c.460-14T>C		intron_variant	Intron 4 of 4	1	NM_002084.5	ENSP00000373477.4	P22352
GPX3	ENST00000520059.1 link	c.224T>C	p.Leu75Ser	missense_variant	Exon 3 of 3	3		ENSP00000429314.1	H0YBE4
GPX3	ENST00000521632.1 link	c.267-14T>C		intron_variant	Intron 2 of 2	5		ENSP00000430743.2	H0YC19
GPX3	ENST00000517973.1 link	c.*3-14T>C		intron_variant	Intron 3 of 3	3		ENSP00000429709.1	A0A182DWH9

Frequencies

GnomAD3 genomes

AF:

0.787

AC:

119651

AN:

151986

Hom.:

47699

Cov.:

show subpopulations

Gnomad AFR

AF:

0.647

Gnomad AMI

AF:

0.947

Gnomad AMR

AF:

0.839

Gnomad ASJ

AF:

0.800

Gnomad EAS

AF:

0.974

Gnomad SAS

AF:

0.836

Gnomad FIN

AF:

0.818

Gnomad MID

AF:

0.829

Gnomad NFE

AF:

0.835

Gnomad OTH

AF:

0.787

GnomAD3 exomes

AF:

0.837

AC:

208560

AN:

249148

Hom.:

87915

AF XY:

0.836

AC XY:

113098

AN XY:

135214

show subpopulations

Gnomad AFR exome

AF:

0.647

Gnomad AMR exome

AF:

0.898

Gnomad ASJ exome

AF:

0.804

Gnomad EAS exome

AF:

0.976

Gnomad SAS exome

AF:

0.829

Gnomad FIN exome

AF:

0.819

Gnomad NFE exome

AF:

0.831

Gnomad OTH exome

AF:

0.834

GnomAD4 exome

AF:

0.834

AC:

1215701

AN:

1457516

Hom.:

508444

Cov.:

AF XY:

0.834

AC XY:

605174

AN XY:

725410

show subpopulations

Gnomad4 AFR exome

AF:

0.646

Gnomad4 AMR exome

AF:

0.890

Gnomad4 ASJ exome

AF:

0.804

Gnomad4 EAS exome

AF:

0.981

Gnomad4 SAS exome

AF:

0.830

Gnomad4 FIN exome

AF:

0.821

Gnomad4 NFE exome

AF:

0.835

Gnomad4 OTH exome

AF:

0.819

GnomAD4 genome

AF:

0.787

AC:

119733

AN:

152104

Hom.:

47735

Cov.:

AF XY:

0.787

AC XY:

58520

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.648

Gnomad4 AMR

AF:

0.839

Gnomad4 ASJ

AF:

0.800

Gnomad4 EAS

AF:

0.974

Gnomad4 SAS

AF:

0.836

Gnomad4 FIN

AF:

0.818

Gnomad4 NFE

AF:

0.835

Gnomad4 OTH

AF:

0.788

Alfa

AF:

0.827

Hom.:

91002

Bravo

AF:

0.782

Asia WGS

AF:

0.860

AC:

2989

AN:

3478

EpiCase

AF:

0.835

EpiControl

AF:

0.835

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.3

DANN

Benign

0.73

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