rs55743914

Positions:

• chr6-127972417-C-T

Variant summary

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

The NM_002844.4(PTPRK):​c.4269+605G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,102 control chromosomes in the GnomAD database, including 2,911 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 0.18 (2911 hom., cov: 32)
• Consequence: PTPRK NM_002844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.335

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=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRK	NM_002844.4	c.4269+605G>A		intron_variant		ENST00000368226.9	NP_002835.2
PTPRK	NM_001135648.3	c.4287+605G>A		intron_variant			NP_001129120.1
PTPRK	NM_001291981.2	c.4335+605G>A		intron_variant			NP_001278910.1
PTPRK	NM_001291984.2	c.4266+605G>A		intron_variant			NP_001278913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRK	ENST00000368226.9	c.4269+605G>A		intron_variant		1	NM_002844.4	ENSP00000357209	P4

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27883 AN: 151984 Hom.: 2908 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0250

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.183 AC: 27895 AN: 152102 Hom.: 2911 Cov.: 32 AF XY: 0.182 AC XY: 13509 AN XY: 74340

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.0251

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.233

Gnomad4 OTH AF: 0.205

Alfa AF: 0.225 Hom.: 830

Bravo AF: 0.184

Asia WGS AF: 0.0980 AC: 341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	14
DANN	Benign	0.80

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: rs55743914; hg19: chr6-128293562;