6-127983343-T-C

Position:

• chr6-127983343-T-C

Variant summary

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

The NM_002844.4(PTPRK):​c.3286A>G​(p.Ile1096Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTPRK NM_002844.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.02

Genes affected

PTPRK (HGNC:9674): (protein tyrosine phosphatase receptor type K) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP possesses an extracellular region, a single transmembrane region, and two tandem catalytic domains, and thus represents a receptor-type PTP. The extracellular region contains a meprin-A5 antigen-PTP mu (MAM) domain, an Ig-like domain and four fibronectin type III-like repeats. This PTP was shown to mediate homophilic intercellular interaction, possibly through the interaction with beta- and gamma-catenin at adherens junctions. Expression of this gene was found to be stimulated by TGF-beta 1, which may be important for the inhibition of keratinocyte proliferation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRK	NM_002844.4	c.3286A>G	p.Ile1096Val	missense_variant	23/30	ENST00000368226.9	NP_002835.2
PTPRK	NM_001291981.2	c.3352A>G	p.Ile1118Val	missense_variant	26/33		NP_001278910.1
PTPRK	NM_001135648.3	c.3304A>G	p.Ile1102Val	missense_variant	24/31		NP_001129120.1
PTPRK	NM_001291984.2	c.3283A>G	p.Ile1095Val	missense_variant	23/30		NP_001278913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRK	ENST00000368226.9	c.3286A>G	p.Ile1096Val	missense_variant	23/30	1	NM_002844.4	ENSP00000357209.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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 09, 2024

The c.3304A>G (p.I1102V) alteration is located in exon 24 (coding exon 24) of the PTPRK gene. This alteration results from a A to G substitution at nucleotide position 3304, causing the isoleucine (I) at amino acid position 1102 to be replaced by a valine (V). 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	0.18
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	.;.;.;T;T;.
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Uncertain	0.093	D
MetaRNN	Uncertain	0.54	D;D;D;D;D;D
MetaSVM	Uncertain	0.35	D
MutationAssessor	Benign	1.2	.;.;.;.;L;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.75	N;N;N;N;N;N
REVEL	Uncertain	0.59
Sift	Uncertain	0.029	D;D;D;D;D;D
Sift4G	Benign	0.14	T;T;T;T;T;T
Polyphen		0.68	P;.;B;.;P;.
Vest4		0.73
MutPred		0.63		.;.;.;.;Loss of stability (P = 0.2885);.;
MVP		0.22
MPC		1.0
ClinPred		0.82	D
GERP RS		5.5
Varity_R		0.28
gMVP		0.34

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-128304488; COSMIC: COSV105297262; COSMIC: COSV105297262;