chr6-127981265-G-C

Position:

• chr6-127981265-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_002844.4(PTPRK):​c.3562C>G​(p.Leu1188Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. 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: 5.01

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, PTPRK
• BP4: Computational evidence support a benign effect (MetaRNN=0.21840993).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRK	NM_002844.4	c.3562C>G	p.Leu1188Val	missense_variant	25/30	ENST00000368226.9
PTPRK	NM_001291981.2	c.3628C>G	p.Leu1210Val	missense_variant	28/33
PTPRK	NM_001135648.3	c.3580C>G	p.Leu1194Val	missense_variant	26/31
PTPRK	NM_001291984.2	c.3559C>G	p.Leu1187Val	missense_variant	25/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRK	ENST00000368226.9	c.3562C>G	p.Leu1188Val	missense_variant	25/30	1	NM_002844.4	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jan 26, 2023

The c.3580C>G (p.L1194V) alteration is located in exon 26 (coding exon 26) of the PTPRK gene. This alteration results from a C to G substitution at nucleotide position 3580, causing the leucine (L) at amino acid position 1194 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	0.10
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Uncertain	1.0
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.22	T;T;T;T;T;T
MetaSVM	Benign	-0.85	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.88	N;N;N;N;N;N
REVEL	Benign	0.093
Sift	Benign	0.31	T;T;T;T;T;T
Sift4G	Benign	0.49	T;T;T;T;T;T
Polyphen		0.051	B;.;P;.;B;.
Vest4		0.32
MutPred		0.27		.;.;.;.;Loss of loop (P = 0.1242);.;
MVP		0.19
MPC		0.62
ClinPred		0.76	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
gMVP		0.47

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: chr6-128302410;