6-128056990-T-G

Variant names:

• chr6-128056990-T-G
• rs10499136
• NM_002844.4:c.2194+7768A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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 -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 rank	MANE	Protein	UniProt
PTPRK	NM_002844.4	c.2194+7768A>C		intron_variant	Intron 13 of 29	ENST00000368226.9	NP_002835.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRK	ENST00000368226.9	c.2194+7768A>C		intron_variant	Intron 13 of 29	1	NM_002844.4	ENSP00000357209.4

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

African (AFR) AF: 0.0339 AC: 1407 AN: 41550

American (AMR) AF: 0.00412 AC: 63 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3470

East Asian (EAS) AF: 0.0566 AC: 293 AN: 5178

South Asian (SAS) AF: 0.0104 AC: 50 AN: 4830

European-Finnish (FIN) AF: 0.0799 AC: 847 AN: 10600

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00209 AC: 142 AN: 68008

Other (OTH) AF: 0.0171 AC: 36 AN: 2110

Alfa AF: 0.0172 Hom.: 25

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
PhyloP100		0.065
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs10499136; hg19: chr6-128378135;