Genetic Variant GPX3:c.87+299G>A (chr5-151021040-G-A) – 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.87+299G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 415,042 control chromosomes in the GnomAD database, including 3,184 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 0.10 ( 886 hom., cov: 32)

Exomes 𝑓: 0.13 ( 2298 hom. )

Consequence

GPX3
NM_002084.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.171

Publications

12 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=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPX3	NM_002084.5 link	c.87+299G>A		intron_variant	Intron 1 of 4	ENST00000388825.9	NP_002075.2	P22352
GPX3	NM_001329790.2 link	c.114+186G>A		intron_variant	Intron 2 of 5		NP_001316719.1	P22352

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPX3	ENST00000388825.9 link	c.87+299G>A		intron_variant	Intron 1 of 4	1	NM_002084.5	ENSP00000373477.4		P22352

Frequencies

GnomAD3 genomes

AF:

0.0999

AC:

15190

AN:

152046

Hom.:

887

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0390

Gnomad AMI

AF:

0.248

Gnomad AMR

AF:

0.0738

Gnomad ASJ

AF:

0.129

Gnomad EAS

AF:

0.153

Gnomad SAS

AF:

0.143

Gnomad FIN

AF:

0.104

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.131

Gnomad OTH

AF:

0.107

GnomAD4 exome

AF:

0.129

AC:

33994

AN:

262878

Hom.:

2298

Cov.:

AF XY:

0.133

AC XY:

18471

AN XY:

139310

show subpopulations

African (AFR)

AF:

0.0482

AC:

315

AN:

6538

American (AMR)

AF:

0.0657

AC:

523

AN:

7960

Ashkenazi Jewish (ASJ)

AF:

0.149

AC:

1232

AN:

8294

East Asian (EAS)

AF:

0.135

AC:

1746

AN:

12936

South Asian (SAS)

AF:

0.155

AC:

5640

AN:

36318

European-Finnish (FIN)

AF:

0.109

AC:

1745

AN:

15992

Middle Eastern (MID)

AF:

0.197

AC:

300

AN:

1520

European-Non Finnish (NFE)

AF:

0.130

AC:

20565

AN:

157758

Other (OTH)

AF:

0.124

AC:

1928

AN:

15562

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1436

2872

4309

5745

7181

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

282

376

470

<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:

0.0998

AC:

15186

AN:

152164

Hom.:

886

Cov.:

AF XY:

0.0982

AC XY:

7303

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.0390

AC:

1622

AN:

41540

American (AMR)

AF:

0.0737

AC:

1126

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.129

AC:

447

AN:

3470

East Asian (EAS)

AF:

0.153

AC:

790

AN:

5150

South Asian (SAS)

AF:

0.143

AC:

692

AN:

4828

European-Finnish (FIN)

AF:

0.104

AC:

1100

AN:

10590

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.131

AC:

8899

AN:

67982

Other (OTH)

AF:

0.105

AC:

222

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

717

1433

2150

2866

3583

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

368

552

736

920

<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:

0.115

Hom.:

1373

Bravo

AF:

0.0924

Asia WGS

AF:

0.128

AC:

447

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.2

(source)

DANN

Benign

0.88

PhyloP100

-0.17

PromoterAI

0.085

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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