chr6-28529583-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001509.3(GPX5):c.220G>T(p.Gly74Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,810 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: 31)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
GPX5
NM_001509.3 missense
NM_001509.3 missense
Scores
5
7
6
Clinical Significance
Conservation
PhyloP100: 5.69
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.911
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GPX5 | NM_001509.3 | c.220G>T | p.Gly74Cys | missense_variant | 2/5 | ENST00000412168.7 | |
GPX5 | NM_003996.3 | c.220G>T | p.Gly74Cys | missense_variant | 2/4 | ||
GPX5 | NR_144470.2 | n.416G>T | non_coding_transcript_exon_variant | 2/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GPX5 | ENST00000412168.7 | c.220G>T | p.Gly74Cys | missense_variant | 2/5 | 1 | NM_001509.3 | P1 | |
GPX5 | ENST00000469384.1 | c.220G>T | p.Gly74Cys | missense_variant | 2/4 | 1 | |||
GPX5 | ENST00000442674.6 | n.475G>T | non_coding_transcript_exon_variant | 2/6 | 5 | ||||
GPX5 | ENST00000483784.1 | n.411G>T | non_coding_transcript_exon_variant | 2/4 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1457810Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 725188
GnomAD4 exome
AF:
AC:
1
AN:
1457810
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
725188
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
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 | Oct 14, 2023 | The c.220G>T (p.G74C) alteration is located in exon 2 (coding exon 2) of the GPX5 gene. This alteration results from a G to T substitution at nucleotide position 220, causing the glycine (G) at amino acid position 74 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Uncertain
D;D
Polyphen
B;.
Vest4
MutPred
Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at