7-143263533-C-T

Variant summary

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

The NM_015917.3(GSTK1):​c.20C>T​(p.Thr7Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000302 in 1,610,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

GSTK1
NM_015917.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0250
Variant links:
Genes affected
GSTK1 (HGNC:16906): (glutathione S-transferase kappa 1) This gene encodes a member of the kappa class of the glutathione transferase superfamily of enzymes that function in cellular detoxification. The encoded protein is localized to the peroxisome and catalyzes the conjugation of glutathione to a wide range of hydrophobic substates facilitating the removal of these compounds from cells. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Jan 2009]
TMEM139-AS1 (HGNC:40988): (TMEM139 antisense RNA 1)

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=0.045620173).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GSTK1NM_015917.3 linkc.20C>T p.Thr7Ile missense_variant Exon 1 of 8 ENST00000358406.10 NP_057001.1 Q9Y2Q3-1Q6FII1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GSTK1ENST00000358406.10 linkc.20C>T p.Thr7Ile missense_variant Exon 1 of 8 1 NM_015917.3 ENSP00000351181.5 Q9Y2Q3-1

Frequencies

GnomAD3 genomes
AF:
0.000131
AC:
20
AN:
152220
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000250
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000133
AC:
33
AN:
248578
Hom.:
0
AF XY:
0.000119
AC XY:
16
AN XY:
134672
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.0000578
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:
0.000247
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000320
AC:
466
AN:
1458242
Hom.:
0
Cov.:
31
AF XY:
0.000309
AC XY:
224
AN XY:
725600
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000201
Gnomad4 NFE exome
AF:
0.000409
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.000131
AC:
20
AN:
152220
Hom.:
0
Cov.:
32
AF XY:
0.000135
AC XY:
10
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000250
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000233
Hom.:
0
Bravo
AF:
0.000110
ExAC
AF:
0.000181
AC:
22
EpiCase
AF:
0.000164
EpiControl
AF:
0.000356

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 21, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.20C>T (p.T7I) alteration is located in exon 1 (coding exon 1) of the GSTK1 gene. This alteration results from a C to T substitution at nucleotide position 20, causing the threonine (T) at amino acid position 7 to be replaced by an isoleucine (I). 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
0.14
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
13
DANN
Benign
0.96
DEOGEN2
Benign
0.095
.;.;T;.
Eigen
Benign
-0.85
Eigen_PC
Benign
-0.85
FATHMM_MKL
Benign
0.071
N
LIST_S2
Benign
0.77
T;T;T;T
M_CAP
Benign
0.0019
T
MetaRNN
Benign
0.046
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
L;L;L;L
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
-1.8
N;N;N;N
REVEL
Benign
0.047
Sift
Benign
0.21
T;T;T;T
Sift4G
Benign
0.33
T;T;T;T
Polyphen
0.029
B;B;B;B
Vest4
0.17
MVP
0.085
MPC
0.35
ClinPred
0.030
T
GERP RS
0.42
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.27
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs200545707; hg19: chr7-142960626; API