chr6-128005131-T-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_002844.4(PTPRK):​c.2447A>T​(p.Asp816Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000621 in 1,610,922 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

PTPRK
NM_002844.4 missense

Scores

13
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.02
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 -4 ACMG points.

BS2
High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PTPRKNM_002844.4 linkuse as main transcriptc.2447A>T p.Asp816Val missense_variant 15/30 ENST00000368226.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PTPRKENST00000368226.9 linkuse as main transcriptc.2447A>T p.Asp816Val missense_variant 15/301 NM_002844.4 P4Q15262-2

Frequencies

GnomAD3 genomes
AF:
0.0000395
AC:
6
AN:
151834
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000242
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:
0.0000737
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000360
AC:
9
AN:
249658
Hom.:
0
AF XY:
0.0000296
AC XY:
4
AN XY:
134946
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000292
Gnomad ASJ exome
AF:
0.0000997
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000532
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.0000644
AC:
94
AN:
1459088
Hom.:
0
Cov.:
31
AF XY:
0.0000661
AC XY:
48
AN XY:
725880
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000225
Gnomad4 ASJ exome
AF:
0.0000385
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000375
Gnomad4 NFE exome
AF:
0.0000775
Gnomad4 OTH exome
AF:
0.0000665
GnomAD4 genome
AF:
0.0000395
AC:
6
AN:
151834
Hom.:
0
Cov.:
31
AF XY:
0.0000270
AC XY:
2
AN XY:
74124
show subpopulations
Gnomad4 AFR
AF:
0.0000242
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:
0.0000737
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000848
Hom.:
0
Bravo
AF:
0.0000264
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.0000549
EpiControl
AF:
0.000119

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 submitterclinical testingAmbry GeneticsSep 15, 2021The c.2447A>T (p.D816V) alteration is located in exon 15 (coding exon 15) of the PTPRK gene. This alteration results from a A to T substitution at nucleotide position 2447, causing the aspartic acid (D) at amino acid position 816 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
Uncertain
0.41
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
0.060
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Benign
0.15
.;.;.;T;T;.;T
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Uncertain
0.96
D
M_CAP
Benign
0.070
D
MetaRNN
Uncertain
0.67
D;D;D;D;D;D;D
MetaSVM
Benign
-0.87
T
MutationAssessor
Benign
1.7
.;.;.;.;L;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D
PrimateAI
Uncertain
0.76
T
PROVEAN
Uncertain
-4.0
D;D;D;D;D;D;D
REVEL
Uncertain
0.44
Sift
Uncertain
0.0010
D;D;D;D;D;D;D
Sift4G
Uncertain
0.0040
D;D;D;D;D;D;.
Polyphen
0.98
D;.;P;.;D;.;.
Vest4
0.89
MVP
0.54
MPC
1.5
ClinPred
0.82
D
GERP RS
5.9
Varity_R
0.63
gMVP
0.76

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: rs146950732; hg19: chr6-128326276; API