Variant 6-127981272-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_002844.4(PTPRK):c.3555C>G(p.Thr1185=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00263 in 1,613,296 control chromosomes in the GnomAD database, including 127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 70 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 57 hom. )

Consequence

PTPRK
NM_002844.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.57

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 Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 6-127981272-G-C is Benign according to our data. Variant chr6-127981272-G-C is described in ClinVar as [Benign]. Clinvar id is 792053.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.57 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0143 (2170/151852) while in subpopulation AFR AF= 0.05 (2068/41368). AF 95% confidence interval is 0.0482. There are 70 homozygotes in gnomad4. There are 1031 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2170 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PTPRK	NM_002844.4 linkuse as main transcript	c.3555C>G	p.Thr1185=	synonymous_variant	25/30	ENST00000368226.9
PTPRK	NM_001291981.2 linkuse as main transcript	c.3621C>G	p.Thr1207=	synonymous_variant	28/33
PTPRK	NM_001135648.3 linkuse as main transcript	c.3573C>G	p.Thr1191=	synonymous_variant	26/31
PTPRK	NM_001291984.2 linkuse as main transcript	c.3552C>G	p.Thr1184=	synonymous_variant	25/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRK	ENST00000368226.9 linkuse as main transcript	c.3555C>G	p.Thr1185=	synonymous_variant	25/30	1	NM_002844.4	P4	Q15262-2

Frequencies

GnomAD3 genomes

AF:

0.0143

AC:

2165

AN:

151734

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0500

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00421

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:

0.000191

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.00368

AC:

922

AN:

250402

Hom.:

AF XY:

0.00264

AC XY:

357

AN XY:

135376

show subpopulations

Gnomad AFR exome

AF:

0.0499

Gnomad AMR exome

AF:

0.00252

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:

0.000150

Gnomad OTH exome

AF:

0.00164

GnomAD4 exome

AF:

0.00141

AC:

2067

AN:

1461444

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

930

AN XY:

727012

show subpopulations

Gnomad4 AFR exome

AF:

0.0498

Gnomad4 AMR exome

AF:

0.00275

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000103

Gnomad4 OTH exome

AF:

0.00248

GnomAD4 genome

AF:

0.0143

AC:

2170

AN:

151852

Hom.:

Cov.:

AF XY:

0.0139

AC XY:

1031

AN XY:

74188

show subpopulations

Gnomad4 AFR

AF:

0.0500

Gnomad4 AMR

AF:

0.00420

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.00473

Hom.:

Bravo

AF:

0.0162

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

8.0

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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