Genetic Variant NM_002084.5:c.87+994T>C (chr5-151021735-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.87+994T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0907 in 152,858 control chromosomes in the GnomAD database, including 1,148 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 0.091 ( 1141 hom., cov: 32)

Exomes 𝑓: 0.096 ( 7 hom. )

Consequence

GPX3
NM_002084.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.46

Publications

25 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=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002084.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPX3	NM_002084.5	MANE Select	c.87+994T>C		intron	N/A	NP_002075.2
	GPX3	NM_001329790.2		c.114+881T>C		intron	N/A	NP_001316719.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GPX3	ENST00000388825.9	TSL:1 MANE Select	c.87+994T>C	intron	N/A	ENSP00000373477.4	P22352
GPX3	ENST00000521650.5	TSL:2	c.114+881T>C	intron	N/A	ENSP00000427873.1	E5RG32
GPX3	ENST00000517973.1	TSL:3	c.87+994T>C	intron	N/A	ENSP00000429709.1	A0A182DWH9

Frequencies

GnomAD3 genomes

AF:

0.0908

AC:

13793

AN:

151956

Hom.:

1142

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0191

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.167

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.417

Gnomad SAS

AF:

0.200

Gnomad FIN

AF:

0.0821

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0839

Gnomad OTH

AF:

0.0999

GnomAD4 exome

AF:

0.0957

AC:

AN:

784

Hom.:

Cov.:

AF XY:

0.0950

AC XY:

AN XY:

400

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.182

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.143

AC:

AN:

East Asian (EAS)

AF:

0.293

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.0400

AC:

AN:

100

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0680

AC:

AN:

500

Other (OTH)

AF:

0.146

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0907

AC:

13788

AN:

152074

Hom.:

1141

Cov.:

AF XY:

0.0958

AC XY:

7120

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.0191

AC:

793

AN:

41484

American (AMR)

AF:

0.167

AC:

2558

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.107

AC:

370

AN:

3470

East Asian (EAS)

AF:

0.417

AC:

2150

AN:

5156

South Asian (SAS)

AF:

0.199

AC:

957

AN:

4814

European-Finnish (FIN)

AF:

0.0821

AC:

871

AN:

10612

Middle Eastern (MID)

AF:

0.0753

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0839

AC:

5700

AN:

67946

Other (OTH)

AF:

0.0989

AC:

209

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

594

1189

1783

2378

2972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

162

324

486

648

810

<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:

0.0848

Hom.:

849

Bravo

AF:

0.0978

Asia WGS

AF:

0.260

AC:

903

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.84

(source)

DANN

Benign

0.85

PhyloP100

-1.5

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over