7-143264575-G-T

Position:

• chr7-143264575-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015917.3(GSTK1):​c.182G>T​(p.Arg61Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GSTK1 NM_015917.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.713

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]

GSTK1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15660572).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTK1	NM_015917.3	c.182G>T	p.Arg61Leu	missense_variant	3/8	ENST00000358406.10	NP_057001.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTK1	ENST00000358406.10	c.182G>T	p.Arg61Leu	missense_variant	3/8	1	NM_015917.3	ENSP00000351181.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 21, 2024

The c.182G>T (p.R61L) alteration is located in exon 3 (coding exon 3) of the GSTK1 gene. This alteration results from a G to T substitution at nucleotide position 182, causing the arginine (R) at amino acid position 61 to be replaced by a leucine (L). 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	0.30
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	13
DANN	Benign	0.80
DEOGEN2	Benign	0.066	T;.;T;.
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.80	T;T;T;T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.16	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	.;L;L;L
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.5	D;D;D;D
REVEL	Benign	0.12
Sift	Benign	0.69	T;T;T;D
Sift4G	Benign	0.35	T;T;T;T
Polyphen		0.024, 0.0010, 0.0020	.;B;B;B
Vest4		0.26, 0.24, 0.28
MutPred		0.46		.;Gain of ubiquitination at K62 (P = 0.0358);Gain of ubiquitination at K62 (P = 0.0358);Gain of ubiquitination at K62 (P = 0.0358);
MVP		0.21
MPC		0.47
ClinPred		0.22	T
GERP RS		-0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.56
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: chr7-142961668;