7-143268104-C-G

Variant names:

• chr7-143268104-C-G
• rs1244359344
• NM_015917.3:c.551C>G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_015917.3(GSTK1):​c.551C>G​(p.Pro184Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 4.43

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)

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.983

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTK1	NM_015917.3	c.551C>G	p.Pro184Arg	missense_variant	Exon 7 of 8	ENST00000358406.10	NP_057001.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTK1	ENST00000358406.10	c.551C>G	p.Pro184Arg	missense_variant	Exon 7 of 8	1	NM_015917.3	ENSP00000351181.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.719C>G (p.P240R) alteration is located in exon 6 (coding exon 6) of the GSTK1 gene. This alteration results from a C to G substitution at nucleotide position 719, causing the proline (P) at amino acid position 240 to be replaced by an arginine (R). 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	0.94
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.42
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.67	.;.;D;.
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Pathogenic	0.98	D;D;D;D
MetaSVM	Uncertain	0.34	D
MutationAssessor	Pathogenic	3.7	.;.;H;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-8.3	D;D;D;D
REVEL	Pathogenic	0.79
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.92
MutPred		0.88		.;.;Gain of catalytic residue at P184 (P = 0.0261);.;
MVP		0.75
MPC		1.1
ClinPred		1.0	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.99
gMVP		1.0

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

Other links and lift over

dbSNP: rs1244359344; hg19: chr7-142965197;