6-127985832-G-A
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_002844.4(PTPRK):c.3140C>T(p.Thr1047Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,613,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
PTPRK
NM_002844.4 missense
NM_002844.4 missense
Scores
7
8
3
Clinical Significance
Conservation
PhyloP100: 10.0
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.882
BS2
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PTPRK | NM_002844.4 | c.3140C>T | p.Thr1047Met | missense_variant | 22/30 | ENST00000368226.9 | NP_002835.2 | |
PTPRK | NM_001291981.2 | c.3206C>T | p.Thr1069Met | missense_variant | 25/33 | NP_001278910.1 | ||
PTPRK | NM_001135648.3 | c.3158C>T | p.Thr1053Met | missense_variant | 23/31 | NP_001129120.1 | ||
PTPRK | NM_001291984.2 | c.3137C>T | p.Thr1046Met | missense_variant | 22/30 | NP_001278913.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152128Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 250940Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135632
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GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461238Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 726870
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152128Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74318
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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 | Oct 30, 2023 | The c.3158C>T (p.T1053M) alteration is located in exon 23 (coding exon 23) of the PTPRK gene. This alteration results from a C to T substitution at nucleotide position 3158, causing the threonine (T) at amino acid position 1053 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
.;.;.;D;D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;.;.;.;M;.
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D
Polyphen
D;.;D;.;D;.
Vest4
MutPred
0.77
.;.;.;.;Gain of catalytic residue at T1046 (P = 0.0311);.;
MVP
MPC
1.3
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at