Variant 6-28533967-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001509.3(GPX5):c.466T>C(p.Cys156Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000105 in 1,426,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

GPX5
NM_001509.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.00

Variant links:

Genes affected

GPX5 (HGNC:4557): (glutathione peroxidase 5) This gene belongs to the glutathione peroxidase family. It is specifically expressed in the epididymis in the mammalian male reproductive tract, and is androgen-regulated. Unlike several other characterized glutathione peroxidases, this enzyme is not a selenoprotein, lacking the selenocysteine residue. Thus, it is selenium-independent, and has been proposed to play a role in protecting the membranes of spermatozoa from the damaging effects of lipid peroxidation and/or preventing premature acrosome reaction. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2016]

GPX5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.788

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GPX5	NM_001509.3 linkuse as main transcript	c.466T>C	p.Cys156Arg	missense_variant	5/5	ENST00000412168.7
GPX5	NM_003996.3 linkuse as main transcript	c.*45T>C		3_prime_UTR_variant	4/4
GPX5	NR_144470.2 linkuse as main transcript	n.544T>C		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPX5	ENST00000412168.7 linkuse as main transcript	c.466T>C	p.Cys156Arg	missense_variant	5/5	1	NM_001509.3	P1	O75715-1
GPX5	ENST00000469384.1 linkuse as main transcript	c.*45T>C		3_prime_UTR_variant	4/4	1			O75715-2
GPX5	ENST00000442674.6 linkuse as main transcript	n.841T>C		non_coding_transcript_exon_variant	6/6	5
GPX5	ENST00000483784.1 linkuse as main transcript	n.539T>C		non_coding_transcript_exon_variant	4/4	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000442

AC:

AN:

226248

Hom.:

AF XY:

0.00000818

AC XY:

AN XY:

122224

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000961

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000105

AC:

AN:

1426552

Hom.:

Cov.:

AF XY:

0.00000990

AC XY:

AN XY:

707092

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:

0.0000137

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 19, 2024

The c.466T>C (p.C156R) alteration is located in exon 5 (coding exon 5) of the GPX5 gene. This alteration results from a T to C substitution at nucleotide position 466, causing the cysteine (C) at amino acid position 156 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

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.039

MetaRNN

Pathogenic

0.79

MetaSVM

Benign

-1.2

MutationAssessor

Pathogenic

3.5

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-7.2

REVEL

Uncertain

0.36

Sift

Benign

0.071

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.66

MutPred

0.49

Gain of disorder (P = 0.0091);

MVP

0.47

MPC

0.84

ClinPred

0.98

GERP RS

4.3

Varity_R

0.88

gMVP

0.78

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