Variant 6-127976706-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002844.4(PTPRK):c.3920T>C(p.Met1307Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,762 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

PTPRK
NM_002844.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.20

Variant links:

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]

PTPRK links:

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ACMG classification

Classification made for transcript

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 link	c.3920T>C	p.Met1307Thr	missense_variant	27/30	ENST00000368226.9	NP_002835.2	Q15262-2Q86WJ2B4DHC3
PTPRK	NM_001291981.2 link	c.3986T>C	p.Met1329Thr	missense_variant	30/33		NP_001278910.1	Q15262-4
PTPRK	NM_001135648.3 link	c.3938T>C	p.Met1313Thr	missense_variant	28/31		NP_001129120.1	Q15262-3
PTPRK	NM_001291984.2 link	c.3917T>C	p.Met1306Thr	missense_variant	27/30		NP_001278913.1	Q15262-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRK	ENST00000368226.9 link	c.3920T>C	p.Met1307Thr	missense_variant	27/30	1	NM_002844.4	ENSP00000357209.4		Q15262-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251170

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135730

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461762

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2024

The c.3938T>C (p.M1313T) alteration is located in exon 28 (coding exon 28) of the PTPRK gene. This alteration results from a T to C substitution at nucleotide position 3938, causing the methionine (M) at amino acid position 1313 to be replaced by a threonine (T). 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

Pathogenic

0.34

BayesDel_noAF

Pathogenic

0.25

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.19

.;.;.;T;T;.

Eigen

Uncertain

0.19

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.051

MetaRNN

Uncertain

0.74

D;D;D;D;D;D

MetaSVM

Benign

-0.43

MutationAssessor

Benign

-0.35

.;.;.;.;N;.

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.5

N;N;N;N;N;N

REVEL

Uncertain

0.63

Sift

Benign

0.32

T;T;T;T;T;T

Sift4G

Benign

0.59

T;T;T;T;T;T

Polyphen

0.89

P;.;B;.;P;.

Vest4

0.81

MutPred

0.48

.;.;.;.;Loss of stability (P = 0.0037);.;

MVP

0.71

MPC

0.60

ClinPred

0.62

GERP RS

5.6

Varity_R

0.29

gMVP

0.42

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over