chr6-28534102-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001509.3(GPX5):​c.601C>T​(p.Arg201Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000614 in 1,611,258 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000058 ( 1 hom. )

Consequence

GPX5
NM_001509.3 missense

Scores

4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0370
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.024207652).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GPX5NM_001509.3 linkc.601C>T p.Arg201Trp missense_variant Exon 5 of 5 ENST00000412168.7 NP_001500.1 O75715-1V9HWN8
GPX5NM_003996.3 linkc.*180C>T 3_prime_UTR_variant Exon 4 of 4 NP_003987.2 O75715-2
GPX5NR_144470.2 linkn.679C>T non_coding_transcript_exon_variant Exon 4 of 4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GPX5ENST00000412168.7 linkc.601C>T p.Arg201Trp missense_variant Exon 5 of 5 1 NM_001509.3 ENSP00000392398.2 O75715-1
GPX5ENST00000442674.6 linkn.976C>T non_coding_transcript_exon_variant Exon 6 of 6 5
GPX5ENST00000469384.1 linkc.*180C>T downstream_gene_variant 1 ENSP00000419935.1 O75715-2
GPX5ENST00000483784.1 linkn.*123C>T downstream_gene_variant 5

Frequencies

GnomAD3 genomes
AF:
0.0000921
AC:
14
AN:
152010
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000766
AC:
19
AN:
248200
Hom.:
0
AF XY:
0.0000670
AC XY:
9
AN XY:
134252
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00152
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000267
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.0000582
AC:
85
AN:
1459248
Hom.:
1
Cov.:
31
AF XY:
0.0000647
AC XY:
47
AN XY:
725950
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00204
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000171
Gnomad4 OTH exome
AF:
0.000216
GnomAD4 genome
AF:
0.0000921
AC:
14
AN:
152010
Hom.:
0
Cov.:
32
AF XY:
0.0000943
AC XY:
7
AN XY:
74250
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000271
Hom.:
0
Bravo
AF:
0.0000756
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.000164
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.601C>T (p.R201W) alteration is located in exon 5 (coding exon 5) of the GPX5 gene. This alteration results from a C to T substitution at nucleotide position 601, causing the arginine (R) at amino acid position 201 to be replaced by a tryptophan (W). 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
Benign
0.18
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
16
DANN
Benign
0.95
DEOGEN2
Benign
0.29
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.072
N
M_CAP
Benign
0.0032
T
MetaRNN
Benign
0.024
T
MetaSVM
Benign
-0.95
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Benign
0.22
T
PROVEAN
Uncertain
-4.2
D
REVEL
Benign
0.0060
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.013
D
Polyphen
0.19
B
Vest4
0.11
MutPred
0.61
Loss of MoRF binding (P = 0.0307);
MVP
0.19
MPC
0.15
ClinPred
0.11
T
GERP RS
-0.35
Varity_R
0.42
gMVP
0.55

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.

Other links and lift over

dbSNP: rs780349667; hg19: chr6-28501879; COSMIC: COSV101297238; COSMIC: COSV101297238; API