6-127989995-T-C

Position:

• chr6-127989995-T-C

Variant summary

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

The ENST00000368226.9(PTPRK):​c.3096+774A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 151,898 control chromosomes in the GnomAD database, including 12,563 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 0.41 (12563 hom., cov: 31)
• Consequence: PTPRK ENST00000368226.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.715

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRK	NM_002844.4	c.3096+774A>G		intron_variant		ENST00000368226.9	NP_002835.2
PTPRK	NM_001135648.3	c.3114+774A>G		intron_variant			NP_001129120.1
PTPRK	NM_001291981.2	c.3162+774A>G		intron_variant			NP_001278910.1
PTPRK	NM_001291984.2	c.3093+774A>G		intron_variant			NP_001278913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRK	ENST00000368226.9	c.3096+774A>G		intron_variant		1	NM_002844.4	ENSP00000357209	P4

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61748 AN: 151780 Hom.: 12549 Cov.: 31

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.407 AC: 61814 AN: 151898 Hom.: 12563 Cov.: 31 AF XY: 0.405 AC XY: 30051 AN XY: 74206

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.387

Alfa AF: 0.411 Hom.: 26143

Bravo AF: 0.409

Asia WGS AF: 0.373 AC: 1298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.3
DANN	Benign	0.44

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: rs9375543; hg19: chr6-128311140; COSMIC: COSV63905723; COSMIC: COSV63905723;