6-127973758-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_002844.4(PTPRK):​c.4039G>A​(p.Gly1347Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,613,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

PTPRK
NM_002844.4 missense

Scores

8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.04
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.1666024).
BS2
High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PTPRKNM_002844.4 linkc.4039G>A p.Gly1347Arg missense_variant Exon 28 of 30 ENST00000368226.9 NP_002835.2 Q15262-2Q86WJ2B4DHC3
PTPRKNM_001291981.2 linkc.4105G>A p.Gly1369Arg missense_variant Exon 31 of 33 NP_001278910.1 Q15262-4
PTPRKNM_001135648.3 linkc.4057G>A p.Gly1353Arg missense_variant Exon 29 of 31 NP_001129120.1 Q15262-3
PTPRKNM_001291984.2 linkc.4036G>A p.Gly1346Arg missense_variant Exon 28 of 30 NP_001278913.1 Q15262-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PTPRKENST00000368226.9 linkc.4039G>A p.Gly1347Arg missense_variant Exon 28 of 30 1 NM_002844.4 ENSP00000357209.4 Q15262-2

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152122
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251148
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135716
show subpopulations
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461742
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727174
show subpopulations
Gnomad4 AFR exome
AF:
0.000119
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:
0.00
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152122
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74318
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000491
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 01, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.4057G>A (p.G1353R) alteration is located in exon 29 (coding exon 29) of the PTPRK gene. This alteration results from a G to A substitution at nucleotide position 4057, causing the glycine (G) at amino acid position 1353 to be replaced by an arginine (R). 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
Uncertain
0.40
BayesDel_addAF
Benign
0.011
T
BayesDel_noAF
Uncertain
-0.040
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
.;.;.;T;T;.
Eigen
Benign
0.018
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Uncertain
0.94
D
M_CAP
Uncertain
0.095
D
MetaRNN
Benign
0.17
T;T;T;T;T;T
MetaSVM
Benign
-0.46
T
MutationAssessor
Benign
-0.65
.;.;.;.;N;.
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-0.94
N;N;N;N;N;N
REVEL
Uncertain
0.35
Sift
Benign
0.43
T;T;T;T;T;T
Sift4G
Benign
0.53
T;T;T;T;T;T
Polyphen
0.062
B;.;P;.;B;.
Vest4
0.30
MutPred
0.32
.;.;.;.;Gain of MoRF binding (P = 0.0062);.;
MVP
0.22
MPC
0.79
ClinPred
0.29
T
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.13
gMVP
0.54

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.

Other links and lift over

dbSNP: rs746283964; hg19: chr6-128294903; API