6-52994200-C-T

Variant summary

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

The NM_001512.4(GSTA4):​c.44G>A​(p.Arg15Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,278 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GSTA4
NM_001512.4 missense

Scores

3
7
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.574
Variant links:
Genes affected
GSTA4 (HGNC:4629): (glutathione S-transferase alpha 4) Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. These enzymes are involved in cellular defense against toxic, carcinogenic, and pharmacologically active electrophilic compounds. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-tranferase belonging to the alpha class. The alpha class genes, which are located in a cluster on chromosome 6, are highly related and encode enzymes with glutathione peroxidase activity that function in the detoxification of lipid peroxidation products. Reactive electrophiles produced by oxidative metabolism have been linked to a number of degenerative diseases including Parkinson's disease, Alzheimer's disease, cataract formation, and atherosclerosis. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

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 Protein UniProt
GSTA4NM_001512.4 linkuse as main transcriptc.44G>A p.Arg15Gln missense_variant 2/7 ENST00000370963.9 NP_001503.1
GSTA4XM_005249035.5 linkuse as main transcriptc.44G>A p.Arg15Gln missense_variant 2/7 XP_005249092.1
GSTA4XM_011514534.4 linkuse as main transcriptc.-16G>A 5_prime_UTR_variant 2/6 XP_011512836.1
GSTA4XM_011514535.4 linkuse as main transcriptc.-16G>A 5_prime_UTR_variant 2/6 XP_011512837.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GSTA4ENST00000370963.9 linkuse as main transcriptc.44G>A p.Arg15Gln missense_variant 2/71 NM_001512.4 ENSP00000360002 P1O15217-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251448
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135898
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461278
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
726978
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000165
AC:
2

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 submitterclinical testingAmbry GeneticsMar 18, 2024The c.44G>A (p.R15Q) alteration is located in exon 2 (coding exon 1) of the GSTA4 gene. This alteration results from a G to A substitution at nucleotide position 44, causing the arginine (R) at amino acid position 15 to be replaced by a glutamine (Q). 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
0.69
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.25
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.29
T;T
Eigen
Uncertain
0.67
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Benign
0.37
N
LIST_S2
Uncertain
0.94
.;D
M_CAP
Benign
0.023
T
MetaRNN
Uncertain
0.46
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Pathogenic
3.7
H;H
MutationTaster
Benign
0.86
D;D;D;D
PrimateAI
Uncertain
0.55
T
PROVEAN
Uncertain
-3.0
D;D
REVEL
Benign
0.28
Sift
Benign
0.052
T;T
Sift4G
Uncertain
0.021
D;D
Polyphen
0.98
D;D
Vest4
0.50
MutPred
0.75
Loss of methylation at R15 (P = 0.012);Loss of methylation at R15 (P = 0.012);
MVP
0.40
MPC
0.57
ClinPred
0.87
D
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.56

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs759677885; hg19: chr6-52858998; COSMIC: COSV63373430; COSMIC: COSV63373430; API