7-143268111-C-T

Variant names:

• chr7-143268111-C-T
• rs143735619
• NM_015917.3:c.558C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_015917.3(GSTK1):​c.558C>T​(p.Thr186Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000326 in 1,613,926 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00019 (1 hom.)
• Consequence: GSTK1 NM_015917.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.74
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 7-143268111-C-T is Benign according to our data. Variant chr7-143268111-C-T is described in ClinVar as Benign. ClinVar VariationId is 726354.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.74 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015917.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTK1	NM_015917.3	MANE Select	c.558C>T	p.Thr186Thr	synonymous	Exon 7 of 8	NP_057001.1	Q9Y2Q3-1
	GSTK1	NM_001143679.2		c.726C>T	p.Thr242Thr	synonymous	Exon 6 of 7	NP_001137151.1	Q9Y2Q3-2
	GSTK1	NM_001143680.2		c.522C>T	p.Thr174Thr	synonymous	Exon 6 of 7	NP_001137152.1	Q9Y2Q3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTK1	ENST00000358406.10	TSL:1 MANE Select	c.558C>T	p.Thr186Thr	synonymous	Exon 7 of 8	ENSP00000351181.5	Q9Y2Q3-1
	GSTK1	ENST00000479303.1	TSL:1	c.726C>T	p.Thr242Thr	synonymous	Exon 6 of 7	ENSP00000431049.1	Q9Y2Q3-2
	GSTK1	ENST00000881234.1		c.726C>T	p.Thr242Thr	synonymous	Exon 6 of 7	ENSP00000551293.1

Frequencies

GnomAD3 genomes AF: 0.00160 AC: 244 AN: 152154 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00553

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.000506 AC: 127 AN: 251058 AF XY: 0.000398

Gnomad AFR exome AF: 0.00498

Gnomad AMR exome AF: 0.000840

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000490

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000529

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000192 AC: 280 AN: 1461654 Hom.: 1 Cov.: 31 AF XY: 0.000169 AC XY: 123 AN XY: 727150

African (AFR) AF: 0.00562 AC: 188 AN: 33472

American (AMR) AF: 0.000850 AC: 38 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39698

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1111894

Other (OTH) AF: 0.000348 AC: 21 AN: 60388

GnomAD4 genome AF: 0.00162 AC: 246 AN: 152272 Hom.: 3 Cov.: 32 AF XY: 0.00172 AC XY: 128 AN XY: 74454

African (AFR) AF: 0.00556 AC: 231 AN: 41562

American (AMR) AF: 0.000654 AC: 10 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68008

Other (OTH) AF: 0.00190 AC: 4 AN: 2108

Alfa AF: 0.00101 Hom.: 1

Bravo AF: 0.00197

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.37
DANN	Benign	0.83
PhyloP100		-4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs143735619; hg19: chr7-142965204;