NM_002844.4:c.1560C>T

Variant names:

• chr6-128083730-G-A
• rs11962559
• NM_002844.4:c.1560C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_002844.4(PTPRK):​c.1560C>T​(p.Ile520Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0054 in 1,591,572 control chromosomes in the GnomAD database, including 431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (221 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (210 hom.)
• Consequence: PTPRK NM_002844.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.41
• Publications: 2 publications found

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-AS1 (HGNC:40484): (PTPRK antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP6: Variant 6-128083730-G-A is Benign according to our data. Variant chr6-128083730-G-A is described in ClinVar as Benign. ClinVar VariationId is 776153.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=3.41 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0987 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRK	NM_002844.4	MANE Select	c.1560C>T	p.Ile520Ile	synonymous	Exon 9 of 30	NP_002835.2
	PTPRK	NM_001291981.2		c.1560C>T	p.Ile520Ile	synonymous	Exon 9 of 33	NP_001278910.1	Q15262-4
	PTPRK	NM_001135648.3		c.1560C>T	p.Ile520Ile	synonymous	Exon 9 of 31	NP_001129120.1	Q15262-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRK	ENST00000368226.9	TSL:1 MANE Select	c.1560C>T	p.Ile520Ile	synonymous	Exon 9 of 30	ENSP00000357209.4	Q15262-2
	PTPRK	ENST00000532331.5	TSL:1	c.1560C>T	p.Ile520Ile	synonymous	Exon 9 of 33	ENSP00000432973.1	Q15262-4
	PTPRK	ENST00000368213.9	TSL:1	c.1560C>T	p.Ile520Ile	synonymous	Exon 9 of 31	ENSP00000357196.5	Q15262-3

Frequencies

GnomAD3 genomes AF: 0.0291 AC: 4423 AN: 151900 Hom.: 218 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00991

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000530

Gnomad OTH AF: 0.0268

GnomAD2 exomes AF: 0.00770 AC: 1885 AN: 244842 AF XY: 0.00579

Gnomad AFR exome AF: 0.105

Gnomad AMR exome AF: 0.00574

Gnomad ASJ exome AF: 0.000403

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000333

Gnomad OTH exome AF: 0.00187

GnomAD4 exome AF: 0.00288 AC: 4145 AN: 1439554 Hom.: 210 Cov.: 28 AF XY: 0.00253 AC XY: 1816 AN XY: 717156

African (AFR) AF: 0.0995 AC: 3236 AN: 32518

American (AMR) AF: 0.00638 AC: 279 AN: 43760

Ashkenazi Jewish (ASJ) AF: 0.000349 AC: 9 AN: 25756

East Asian (EAS) AF: 0.00 AC: 0 AN: 38988

South Asian (SAS) AF: 0.000165 AC: 14 AN: 84724

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53120

Middle Eastern (MID) AF: 0.00474 AC: 27 AN: 5698

European-Non Finnish (NFE) AF: 0.000193 AC: 211 AN: 1095518

Other (OTH) AF: 0.00619 AC: 368 AN: 59472

GnomAD4 genome AF: 0.0292 AC: 4446 AN: 152018 Hom.: 221 Cov.: 32 AF XY: 0.0281 AC XY: 2084 AN XY: 74286

African (AFR) AF: 0.101 AC: 4198 AN: 41478

American (AMR) AF: 0.00990 AC: 151 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000530 AC: 36 AN: 67934

Other (OTH) AF: 0.0266 AC: 56 AN: 2108

Alfa AF: 0.00876 Hom.: 98

Bravo AF: 0.0328

Asia WGS AF: 0.00896 AC: 32 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	17
DANN	Benign	0.76
PhyloP100		3.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11962559; hg19: chr6-128404875;