1-52602481-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_015696.5(GPX7):​c.72C>G​(p.Asp24Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,405,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GPX7
NM_015696.5 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.03
Variant links:
Genes affected
GPX7 (HGNC:4559): (glutathione peroxidase 7) Enables catalase activity. Predicted to be involved in cellular response to oxidative stress. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.34317046).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GPX7NM_015696.5 linkc.72C>G p.Asp24Glu missense_variant Exon 1 of 3 ENST00000361314.5 NP_056511.2 Q96SL4
GPX7XM_047418560.1 linkc.-1085C>G 5_prime_UTR_variant Exon 1 of 3 XP_047274516.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GPX7ENST00000361314.5 linkc.72C>G p.Asp24Glu missense_variant Exon 1 of 3 1 NM_015696.5 ENSP00000354677.4 Q96SL4
GPX7ENST00000459779.1 linkn.82C>G non_coding_transcript_exon_variant Exon 1 of 2 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000142
AC:
2
AN:
1405018
Hom.:
0
Cov.:
32
AF XY:
0.00000143
AC XY:
1
AN XY:
697450
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:
0.00000184
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 13, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.72C>G (p.D24E) alteration is located in exon 1 (coding exon 1) of the GPX7 gene. This alteration results from a C to G substitution at nucleotide position 72, causing the aspartic acid (D) at amino acid position 24 to be replaced by a glutamic acid (E). 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
Uncertain
0.56
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.13
T
Eigen
Benign
0.093
Eigen_PC
Benign
0.17
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.72
T
M_CAP
Uncertain
0.14
D
MetaRNN
Benign
0.34
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.71
N
PrimateAI
Pathogenic
0.90
D
PROVEAN
Benign
-1.8
N
REVEL
Benign
0.083
Sift
Uncertain
0.025
D
Sift4G
Benign
0.080
T
Polyphen
0.71
P
Vest4
0.55
MutPred
0.36
Loss of ubiquitination at K29 (P = 0.1601);
MVP
0.46
MPC
0.37
ClinPred
0.80
D
GERP RS
3.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.52
gMVP
0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-53068153; API