rs10485162

Variant names:

• chr6-128276846-C-T
• rs10485162
• NM_002844.4:c.496-34244G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002844.4(PTPRK):​c.496-34244G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0193 in 152,172 control chromosomes in the GnomAD database, including 76 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 (76 hom., cov: 32)
• Consequence: PTPRK NM_002844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0193 (2943/152172) while in subpopulation AFR AF = 0.0395 (1641/41534). AF 95% confidence interval is 0.0379. There are 76 homozygotes in GnomAd4. There are 1648 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2943 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRK	NM_002844.4	c.496-34244G>A		intron_variant	Intron 3 of 29	ENST00000368226.9	NP_002835.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRK	ENST00000368226.9	c.496-34244G>A		intron_variant	Intron 3 of 29	1	NM_002844.4	ENSP00000357209.4

Frequencies

GnomAD3 genomes AF: 0.0193 AC: 2939 AN: 152054 Hom.: 76 Cov.: 32

Gnomad AFR AF: 0.0396

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00879

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.0375

Gnomad SAS AF: 0.00849

Gnomad FIN AF: 0.0737

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00179

Gnomad OTH AF: 0.0124

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

GnomAD4 genome AF: 0.0193 AC: 2943 AN: 152172 Hom.: 76 Cov.: 32 AF XY: 0.0222 AC XY: 1648 AN XY: 74386

African (AFR) AF: 0.0395 AC: 1641 AN: 41534

American (AMR) AF: 0.00878 AC: 134 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.0376 AC: 195 AN: 5182

South Asian (SAS) AF: 0.00829 AC: 40 AN: 4824

European-Finnish (FIN) AF: 0.0737 AC: 780 AN: 10588

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

European-Non Finnish (NFE) AF: 0.00179 AC: 122 AN: 67998

Other (OTH) AF: 0.0133 AC: 28 AN: 2112

Alfa AF: 0.0132 Hom.: 6

Bravo AF: 0.0160

Asia WGS AF: 0.0380 AC: 133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.84
DANN	Benign	0.52
PhyloP100		-0.38
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: rs10485162; hg19: chr6-128597991;