rs10499136

Positions:

• chr6-128056990-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002844.4(PTPRK):​c.2194+7768A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0187 in 152,246 control chromosomes in the GnomAD database, including 77 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 0.019 (77 hom., cov: 32)
• Consequence: PTPRK NM_002844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRK	NM_002844.4	c.2194+7768A>C		intron_variant		ENST00000368226.9	NP_002835.2
PTPRK-AS1	NR_125849.1	n.60-5712T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRK	ENST00000368226.9	c.2194+7768A>C		intron_variant		1	NM_002844.4	ENSP00000357209	P4
PTPRK-AS1	ENST00000417390.1	n.39-5712T>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0187 AC: 2848 AN: 152128 Hom.: 77 Cov.: 32

Gnomad AFR AF: 0.0338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00412

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.0565

Gnomad SAS AF: 0.0106

Gnomad FIN AF: 0.0799

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00209

Gnomad OTH AF: 0.0168

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

GnomAD4 genome AF: 0.0187 AC: 2853 AN: 152246 Hom.: 77 Cov.: 32 AF XY: 0.0218 AC XY: 1622 AN XY: 74420

Gnomad4 AFR AF: 0.0339

Gnomad4 AMR AF: 0.00412

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.0566

Gnomad4 SAS AF: 0.0104

Gnomad4 FIN AF: 0.0799

Gnomad4 NFE AF: 0.00209

Gnomad4 OTH AF: 0.0171

Alfa AF: 0.0124 Hom.: 7

Bravo AF: 0.0147

Asia WGS AF: 0.0370 AC: 128 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.55

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

Other links and lift over

dbSNP: rs10499136; hg19: chr6-128378135;