dbSNP rs8177412: GPX3:c.-129T>C (chr5-151020526-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002084.5(GPX3):c.-129T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 728,610 control chromosomes in the GnomAD database, including 7,191 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 0.15 ( 1861 hom., cov: 33)

Exomes 𝑓: 0.13 ( 5330 hom. )

Consequence

GPX3
NM_002084.5 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.152

Publications

34 publications found

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 was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPX3	NM_002084.5 link	c.-129T>C		upstream_gene_variant		ENST00000388825.9	NP_002075.2	P22352
GPX3	NM_001329790.2 link	c.-129T>C		upstream_gene_variant			NP_001316719.1	P22352

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPX3	ENST00000388825.9 link	c.-129T>C		upstream_gene_variant		1	NM_002084.5	ENSP00000373477.4		P22352

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

23040

AN:

152154

Hom.:

1858

Cov.:

show subpopulations

Gnomad AFR

AF:

0.204

Gnomad AMI

AF:

0.248

Gnomad AMR

AF:

0.0968

Gnomad ASJ

AF:

0.124

Gnomad EAS

AF:

0.172

Gnomad SAS

AF:

0.161

Gnomad FIN

AF:

0.112

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.141

GnomAD4 exome

AF:

0.133

AC:

76889

AN:

576338

Hom.:

5330

Cov.:

AF XY:

0.135

AC XY:

39814

AN XY:

294246

show subpopulations

African (AFR)

AF:

0.207

AC:

2773

AN:

13366

American (AMR)

AF:

0.0819

AC:

1187

AN:

14486

Ashkenazi Jewish (ASJ)

AF:

0.136

AC:

1894

AN:

13906

East Asian (EAS)

AF:

0.142

AC:

3942

AN:

27718

South Asian (SAS)

AF:

0.168

AC:

7147

AN:

42530

European-Finnish (FIN)

AF:

0.115

AC:

3436

AN:

29912

Middle Eastern (MID)

AF:

0.192

AC:

420

AN:

2184

European-Non Finnish (NFE)

AF:

0.129

AC:

51999

AN:

402380

Other (OTH)

AF:

0.137

AC:

4091

AN:

29856

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

3386

6772

10159

13545

16931

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1158

2316

3474

4632

5790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.151

AC:

23065

AN:

152272

Hom.:

1861

Cov.:

AF XY:

0.149

AC XY:

11068

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.204

AC:

8478

AN:

41542

American (AMR)

AF:

0.0967

AC:

1480

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.124

AC:

432

AN:

3470

East Asian (EAS)

AF:

0.172

AC:

893

AN:

5180

South Asian (SAS)

AF:

0.161

AC:

779

AN:

4830

European-Finnish (FIN)

AF:

0.112

AC:

1187

AN:

10608

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.136

AC:

9234

AN:

68008

Other (OTH)

AF:

0.139

AC:

295

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1043

2086

3130

4173

5216

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

260

520

780

1040

1300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.139

Hom.:

4123

Bravo

AF:

0.150

Asia WGS

AF:

0.154

AC:

536

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

(source)

DANN

Benign

0.25

PhyloP100

0.15

PromoterAI

-0.031

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over