Genetic Variant GPX3:c.87+2032C>T (chr5-151022773-C-T) – 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+2032C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 152,032 control chromosomes in the GnomAD database, including 31,125 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 0.62 ( 31125 hom., cov: 31)

Consequence

GPX3
NM_002084.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.76

Publications

22 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=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPX3	NM_002084.5 link	c.87+2032C>T		intron_variant	Intron 1 of 4	ENST00000388825.9	NP_002075.2	P22352
GPX3	NM_001329790.2 link	c.114+1919C>T		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+2032C>T		intron_variant	Intron 1 of 4	1	NM_002084.5	ENSP00000373477.4		P22352

Frequencies

GnomAD3 genomes

AF:

0.618

AC:

93906

AN:

151914

Hom.:

31115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.368

Gnomad AMI

AF:

0.772

Gnomad AMR

AF:

0.648

Gnomad ASJ

AF:

0.686

Gnomad EAS

AF:

0.517

Gnomad SAS

AF:

0.533

Gnomad FIN

AF:

0.729

Gnomad MID

AF:

0.690

Gnomad NFE

AF:

0.754

Gnomad OTH

AF:

0.627

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.618

AC:

93951

AN:

152032

Hom.:

31125

Cov.:

AF XY:

0.613

AC XY:

45542

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.368

AC:

15272

AN:

41446

American (AMR)

AF:

0.648

AC:

9902

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.686

AC:

2381

AN:

3472

East Asian (EAS)

AF:

0.517

AC:

2672

AN:

5168

South Asian (SAS)

AF:

0.534

AC:

2570

AN:

4810

European-Finnish (FIN)

AF:

0.729

AC:

7715

AN:

10578

Middle Eastern (MID)

AF:

0.684

AC:

201

AN:

294

European-Non Finnish (NFE)

AF:

0.754

AC:

51216

AN:

67968

Other (OTH)

AF:

0.626

AC:

1318

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1605

3210

4816

6421

8026

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

758

1516

2274

3032

3790

<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:

0.703

Hom.:

49348

Bravo

AF:

0.599

Asia WGS

AF:

0.516

AC:

1793

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.8

(source)

DANN

Benign

0.85

PhyloP100

-1.8

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over