rs10499137

chr6-128101554-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002844.4(PTPRK):c.1163-11562T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 152,140 control chromosomes in the GnomAD database, including 159 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 0.035 (159 hom., cov: 32)
• Consequence: PTPRK NM_002844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.364

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0345 (5252/152140) while in subpopulation EAS AF= 0.0463 (240/5186). AF 95% confidence interval is 0.0415. There are 159 homozygotes in gnomad4. There are 2762 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 5248 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRK	NM_002844.4	c.1163-11562T>C		intron_variant		ENST00000368226.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRK	ENST00000368226.9	c.1163-11562T>C		intron_variant		1	NM_002844.4	P4

Frequencies

GnomAD3 genomes AF: 0.0345 AC: 5248 AN: 152022 Hom.: 159 Cov.: 32

Gnomad AFR AF: 0.00707

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.0217

Gnomad ASJ AF: 0.0450

Gnomad EAS AF: 0.0462

Gnomad SAS AF: 0.0442

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0392

Gnomad OTH AF: 0.0326

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

GnomAD4 genome AF: 0.0345 AC: 5252 AN: 152140 Hom.: 159 Cov.: 32 AF XY: 0.0372 AC XY: 2762 AN XY: 74346

Gnomad4 AFR AF: 0.00715

Gnomad4 AMR AF: 0.0218

Gnomad4 ASJ AF: 0.0450

Gnomad4 EAS AF: 0.0463

Gnomad4 SAS AF: 0.0442

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.0392

Gnomad4 OTH AF: 0.0332

Alfa AF: 0.0384 Hom.: 23

Bravo AF: 0.0273

Asia WGS AF: 0.0640 AC: 223 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.53
Dann	Benign	0.63

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: rs10499137; hg19: chr6-128422699;