3-49357741-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000581.4(GPX1):c.259G>A(p.Ala87Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000293 in 1,603,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A87P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

GPX1
NM_000581.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.289

Publications

3 publications found

Variant links:

Genes affected

GPX1 (HGNC:4553): (glutathione peroxidase 1) 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. Other studies indicate that H2O2 is also essential for growth-factor mediated signal transduction, mitochondrial function, and maintenance of thiol redox-balance; therefore, by limiting H2O2 accumulation, glutathione peroxidases are also involved in modulating these processes. Several isozymes of this gene family exist in vertebrates, which vary in cellular location and substrate specificity. This isozyme is the most abundant, is ubiquitously expressed and localized in the cytoplasm, and whose preferred substrate is hydrogen peroxide. It 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. This gene contains an in-frame GCG trinucleotide repeat in the coding region, and three alleles with 4, 5 or 6 repeats have been found in the human population. The allele with 4 GCG repeats has been significantly associated with breast cancer risk in premenopausal women. Alternatively spliced transcript variants have been found for this gene. Pseudogenes of this locus have been identified on chromosomes X and 21. [provided by RefSeq, Aug 2017]

GPX1 links:

ENSG00000290318 (HGNC:):

ENSG00000290318 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08595094).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000581.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPX1	NM_000581.4	MANE Select	c.259G>A	p.Ala87Thr	missense	Exon 2 of 2	NP_000572.2
GPX1	NM_001329503.2		c.278G>A	p.Arg93His	missense	Exon 2 of 2	NP_001316432.1
GPX1	NM_001329455.2		c.121G>A	p.Ala41Thr	missense	Exon 2 of 2	NP_001316384.1	A0A2R8Y6B6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPX1	ENST00000419783.3	TSL:1 MANE Select	c.259G>A	p.Ala87Thr	missense	Exon 2 of 2	ENSP00000407375.1	P07203-1
ENSG00000290318	ENST00000704381.1		c.471G>A	p.Thr157Thr	synonymous	Exon 6 of 6	ENSP00000515884.1	A0A994J514
GPX1	ENST00000703795.1		c.256G>A	p.Ala86Thr	missense	Exon 2 of 2	ENSP00000515480.1	A0A994J430

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000410

AC:

AN:

244000

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000911

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000262

AC:

AN:

1451842

Hom.:

Cov.:

AF XY:

0.0000292

AC XY:

AN XY:

720166

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33294

American (AMR)

AF:

0.00

AC:

AN:

44492

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25968

East Asian (EAS)

AF:

0.00

AC:

AN:

39436

South Asian (SAS)

AF:

0.0000233

AC:

AN:

85996

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52332

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.0000317

AC:

AN:

1104702

Other (OTH)

AF:

0.0000167

AC:

AN:

59882

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0000592

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41410

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000604

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.066

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.71

MetaRNN

Benign

0.086

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.81

PhyloP100

0.29

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.1

REVEL

Benign

0.037

Sift

Benign

0.49

Sift4G

Benign

0.23

Polyphen

0.13

Vest4

0.025

MutPred

0.52

Loss of glycosylation at K88 (P = 0.1258)

MVP

0.32

MPC

0.63

ClinPred

0.084

GERP RS

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.12

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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