Genetic Variant PTPRK:c.3096+774A>G (chr6-127989995-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002844.4(PTPRK):c.3096+774A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 151,898 control chromosomes in the GnomAD database, including 12,563 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.41 ( 12563 hom., cov: 31)

Consequence

PTPRK
NM_002844.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.715

Publications

4 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002844.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PTPRK	NM_002844.4	MANE Select	c.3096+774A>G	intron	N/A	NP_002835.2
PTPRK	NM_001291981.2		c.3162+774A>G	intron	N/A	NP_001278910.1
PTPRK	NM_001135648.3		c.3114+774A>G	intron	N/A	NP_001129120.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PTPRK	ENST00000368226.9	TSL:1 MANE Select	c.3096+774A>G	intron	N/A	ENSP00000357209.4
PTPRK	ENST00000532331.5	TSL:1	c.3162+774A>G	intron	N/A	ENSP00000432973.1
PTPRK	ENST00000368213.9	TSL:1	c.3114+774A>G	intron	N/A	ENSP00000357196.5

Frequencies

GnomAD3 genomes

AF:

0.407

AC:

61748

AN:

151780

Hom.:

12549

Cov.:

show subpopulations

Gnomad AFR

AF:

0.390

Gnomad AMI

AF:

0.429

Gnomad AMR

AF:

0.404

Gnomad ASJ

AF:

0.455

Gnomad EAS

AF:

0.435

Gnomad SAS

AF:

0.358

Gnomad FIN

AF:

0.434

Gnomad MID

AF:

0.296

Gnomad NFE

AF:

0.413

Gnomad OTH

AF:

0.390

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.407

AC:

61814

AN:

151898

Hom.:

12563

Cov.:

AF XY:

0.405

AC XY:

30051

AN XY:

74206

show subpopulations

African (AFR)

AF:

0.390

AC:

16170

AN:

41430

American (AMR)

AF:

0.405

AC:

6174

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.455

AC:

1578

AN:

3468

East Asian (EAS)

AF:

0.436

AC:

2246

AN:

5156

South Asian (SAS)

AF:

0.358

AC:

1726

AN:

4818

European-Finnish (FIN)

AF:

0.434

AC:

4578

AN:

10544

Middle Eastern (MID)

AF:

0.301

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.413

AC:

28047

AN:

67920

Other (OTH)

AF:

0.387

AC:

816

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1898

3797

5695

7594

9492

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

604

1208

1812

2416

3020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.412

Hom.:

54769

Bravo

AF:

0.409

Asia WGS

AF:

0.373

AC:

1298

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

2.3

(source)

DANN

Benign

0.44

PhyloP100

-0.71

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over