rs1050450

Positions:

chr3-49357401-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000581.4(GPX1):c.599C>T(p.Pro200Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,607,594 control chromosomes in the GnomAD database, including 76,163 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7172 hom., cov: 30)

Exomes 𝑓: 0.30 ( 68991 hom. )

Consequence

GPX1
NM_000581.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.39

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.634427E-4).

BP6

Variant 3-49357401-G-A is Benign according to our data. Variant chr3-49357401-G-A is described in ClinVar as [Benign]. Clinvar id is 16082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-49357401-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPX1	NM_000581.4 linkuse as main transcript	c.599C>T	p.Pro200Leu	missense_variant	2/2	ENST00000419783.3	NP_000572.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPX1	ENST00000419783.3 linkuse as main transcript	c.599C>T	p.Pro200Leu	missense_variant	2/2	1	NM_000581.4	ENSP00000407375	P3	P07203-1

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

45043

AN:

151596

Hom.:

7165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.292

Gnomad AMI

AF:

0.198

Gnomad AMR

AF:

0.220

Gnomad ASJ

AF:

0.461

Gnomad EAS

AF:

0.0578

Gnomad SAS

AF:

0.226

Gnomad FIN

AF:

0.472

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.306

Gnomad OTH

AF:

0.299

GnomAD3 exomes

AF:

0.280

AC:

68269

AN:

244032

Hom.:

11117

AF XY:

0.283

AC XY:

37740

AN XY:

133308

show subpopulations

Gnomad AFR exome

AF:

0.291

Gnomad AMR exome

AF:

0.156

Gnomad ASJ exome

AF:

0.455

Gnomad EAS exome

AF:

0.0559

Gnomad SAS exome

AF:

0.237

Gnomad FIN exome

AF:

0.465

Gnomad NFE exome

AF:

0.312

Gnomad OTH exome

AF:

0.302

GnomAD4 exome

AF:

0.300

AC:

436513

AN:

1455880

Hom.:

68991

Cov.:

AF XY:

0.299

AC XY:

215897

AN XY:

723240

show subpopulations

Gnomad4 AFR exome

AF:

0.294

Gnomad4 AMR exome

AF:

0.164

Gnomad4 ASJ exome

AF:

0.455

Gnomad4 EAS exome

AF:

0.0631

Gnomad4 SAS exome

AF:

0.243

Gnomad4 FIN exome

AF:

0.454

Gnomad4 NFE exome

AF:

0.307

Gnomad4 OTH exome

AF:

0.304

GnomAD4 genome

AF:

0.297

AC:

45072

AN:

151714

Hom.:

7172

Cov.:

AF XY:

0.299

AC XY:

22165

AN XY:

74098

show subpopulations

Gnomad4 AFR

AF:

0.292

Gnomad4 AMR

AF:

0.219

Gnomad4 ASJ

AF:

0.461

Gnomad4 EAS

AF:

0.0581

Gnomad4 SAS

AF:

0.226

Gnomad4 FIN

AF:

0.472

Gnomad4 NFE

AF:

0.306

Gnomad4 OTH

AF:

0.297

Alfa

AF:

0.322

Hom.:

2756

Bravo

AF:

0.277

ESP6500AA

AF:

0.273

AC:

983

ESP6500EA

AF:

0.294

AC:

2330

ExAC

AF:

0.276

AC:

33009

Asia WGS

AF:

0.149

AC:

524

AN:

3478

EpiCase

AF:

0.317

EpiControl

AF:

0.312

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 27592002, 30256368, 22139612, 21636625, 18563616, 29411539, 11103801, 19826042, 22888637, 20178852, 21165435, 16287877, 20441054, 16956821, 21993316, 19415410, 23073788, 15331559, 16945136, 25047527) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

GLUTATHIONE PEROXIDASE POLYMORPHISM

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Jan 01, 1999

- -

Gluthathione peroxidase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.039

T;.;.

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.68

T;T;T

MetaRNN

Benign

0.00056

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.34

N;.;.

MutationTaster

Benign

0.079

P;P

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.1

N;.;.

REVEL

Benign

0.083

Sift

Benign

0.036

D;.;.

Sift4G

Uncertain

0.060

T;T;.

Polyphen

0.0

B;.;.

Vest4

0.094

MPC

0.79

ClinPred

0.012

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.072

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over