7-143268160-A-C

Variant names:

• chr7-143268160-A-C
• rs772501565
• NM_015917.3:c.607A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015917.3(GSTK1):​c.607A>C​(p.Met203Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000057 in 1,613,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000060 (0 hom.)
• Consequence: GSTK1 NM_015917.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.403
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.104424804).

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.607A>C	p.Met203Leu	missense	Exon 7 of 8	NP_057001.1	Q9Y2Q3-1
	GSTK1	NM_001143679.2		c.775A>C	p.Met259Leu	missense	Exon 6 of 7	NP_001137151.1	Q9Y2Q3-2
	GSTK1	NM_001143680.2		c.571A>C	p.Met191Leu	missense	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.607A>C	p.Met203Leu	missense	Exon 7 of 8	ENSP00000351181.5	Q9Y2Q3-1
	GSTK1	ENST00000479303.1	TSL:1	c.775A>C	p.Met259Leu	missense	Exon 6 of 7	ENSP00000431049.1	Q9Y2Q3-2
	GSTK1	ENST00000881234.1		c.775A>C	p.Met259Leu	missense	Exon 6 of 7	ENSP00000551293.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152122 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000441

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251242 AF XY: 0.0000295

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000595 AC: 87 AN: 1461752 Hom.: 0 Cov.: 31 AF XY: 0.0000619 AC XY: 45 AN XY: 727180

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000782 AC: 87 AN: 1111950

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152122 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74324

African (AFR) AF: 0.0000241 AC: 1 AN: 41414

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68024

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.0000565 Hom.: 0

Bravo AF: 0.0000189

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	11
DANN	Benign	0.80
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.10	N
PhyloP100		0.40
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.044
Sift	Benign	0.69	T
Sift4G	Benign	0.60	T
Polyphen		0.0010	B
Vest4		0.25
MutPred		0.68		Loss of catalytic residue at M203 (P = 0.0194)
MVP		0.14
MPC		0.29
ClinPred		0.019	T
GERP RS		0.15
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.099
gMVP		0.86
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs772501565; hg19: chr7-142965253;