Genetic Variant GPX3:c.*138T>G (chr5-151028268-T-G) – 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.*138T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0309 in 750,716 control chromosomes in the GnomAD database, including 1,315 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 0.056 ( 602 hom., cov: 33)

Exomes 𝑓: 0.024 ( 713 hom. )

Consequence

GPX3
NM_002084.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.426

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=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPX3	NM_002084.5 link	c.*138T>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000388825.9	NP_002075.2	P22352
GPX3	NM_001329790.2 link	c.*138T>G		3_prime_UTR_variant	Exon 6 of 6		NP_001316719.1	P22352

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GPX3	ENST00000388825.9 link	c.*138T>G	3_prime_UTR_variant	Exon 5 of 5	1	NM_002084.5	ENSP00000373477.4	P22352
GPX3	ENST00000521632.1 link	c.*104T>G	3_prime_UTR_variant	Exon 3 of 3	5		ENSP00000430743.2	H0YC19
GPX3	ENST00000517973.1 link	c.*362T>G	downstream_gene_variant		3		ENSP00000429709.1	A0A182DWH9

Frequencies

GnomAD3 genomes

AF:

0.0559

AC:

8508

AN:

152142

Hom.:

602

Cov.:

show subpopulations

Gnomad AFR

AF:

0.164

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0290

Gnomad ASJ

AF:

0.0173

Gnomad EAS

AF:

0.0223

Gnomad SAS

AF:

0.0974

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00734

Gnomad OTH

AF:

0.0455

GnomAD4 exome

AF:

0.0245

AC:

14652

AN:

598456

Hom.:

713

Cov.:

AF XY:

0.0270

AC XY:

8433

AN XY:

312808

show subpopulations

Gnomad4 AFR exome

AF:

0.159

Gnomad4 AMR exome

AF:

0.0201

Gnomad4 ASJ exome

AF:

0.0199

Gnomad4 EAS exome

AF:

0.0783

Gnomad4 SAS exome

AF:

0.0891

Gnomad4 FIN exome

AF:

0.00131

Gnomad4 NFE exome

AF:

0.00715

Gnomad4 OTH exome

AF:

0.0293

GnomAD4 genome

AF:

0.0560

AC:

8525

AN:

152260

Hom.:

602

Cov.:

AF XY:

0.0552

AC XY:

4113

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.164

Gnomad4 AMR

AF:

0.0289

Gnomad4 ASJ

AF:

0.0173

Gnomad4 EAS

AF:

0.0224

Gnomad4 SAS

AF:

0.0971

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.00734

Gnomad4 OTH

AF:

0.0450

Alfa

AF:

0.0150

Hom.:

137

Bravo

AF:

0.0605

Asia WGS

AF:

0.0640

AC:

224

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.7

DANN

Benign

0.53

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