Variant 6-28510759-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_182701.1(GPX6):c.233A>G(p.Gln78Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,613,406 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GPX6
NM_182701.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.46

Variant links:

Genes affected

GPX6 (HGNC:4558): (glutathione peroxidase 6) The protein encoded by this gene belongs to the glutathione peroxidase family, members of which catalyze the reduction of hydrogen peroxide, organic hydroperoxides and lipid hydroperoxides, and thereby protect cells against oxidative damage. Several isozymes of this gene family exist in vertebrates, which vary in cellular location and substrate specificity. Expression of this gene has been observed in embryos and olfactory epithelium; however, the exact function of this gene is not known. This isozyme is a selenoprotein in humans, 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. The orthologs of this gene in mouse and rat (and some other species) contain a cysteine (Cys) residue in place of the Sec residue, and their corresponding mRNAs lack SECIS element. [provided by RefSeq, Jul 2017]

GPX6 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPX6	NM_182701.1 linkuse as main transcript	c.233A>G	p.Gln78Arg	missense_variant	2/5	ENST00000361902.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GPX6	ENST00000361902.5 linkuse as main transcript	c.233A>G	p.Gln78Arg	missense_variant	2/5	1	NM_182701.1	P1
GPX6	ENST00000474923.1 linkuse as main transcript	c.233A>G	p.Gln78Arg	missense_variant	2/4	1
GPX6	ENST00000483058.1 linkuse as main transcript	n.452A>G		non_coding_transcript_exon_variant	4/5	4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461234

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726894

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000371

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 06, 2023

The c.233A>G (p.Q78R) alteration is located in exon 2 (coding exon 2) of the GPX6 gene. This alteration results from a A to G substitution at nucleotide position 233, causing the glutamine (Q) at amino acid position 78 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.075

T;.;.

Eigen

Uncertain

0.33

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.72

T;T;.

MetaRNN

Uncertain

0.46

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.3

M;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.4

N;.;D

REVEL

Benign

0.28

Sift

Benign

0.94

T;.;D

Sift4G

Benign

0.47

T;T;D

Polyphen

0.86

P;.;.

Vest4

0.64

MutPred

0.70

Loss of catalytic residue at Q78 (P = 0.1138);.;Loss of catalytic residue at Q78 (P = 0.1138);

MVP

0.28

MPC

0.39

ClinPred

0.52

GERP RS

2.9

Varity_R

0.057

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

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