chr6-128073744-T-C

Position:

• chr6-128073744-T-C

Variant summary

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

The NM_002844.4(PTPRK):​c.1883+5069A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.83 in 151,942 control chromosomes in the GnomAD database, including 52,565 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 0.83 (52565 hom., cov: 31)
• Consequence: PTPRK NM_002844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRK	NM_002844.4	c.1883+5069A>G		intron_variant		ENST00000368226.9	NP_002835.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRK	ENST00000368226.9	c.1883+5069A>G		intron_variant		1	NM_002844.4	ENSP00000357209.4

Frequencies

GnomAD3 genomes AF: 0.831 AC: 126091 AN: 151824 Hom.: 52530 Cov.: 31

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.866

Gnomad AMR AF: 0.879

Gnomad ASJ AF: 0.912

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.974

Gnomad FIN AF: 0.868

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.831

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

GnomAD4 genome AF: 0.830 AC: 126184 AN: 151942 Hom.: 52565 Cov.: 31 AF XY: 0.838 AC XY: 62226 AN XY: 74266

Gnomad4 AFR AF: 0.816

Gnomad4 AMR AF: 0.879

Gnomad4 ASJ AF: 0.912

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.974

Gnomad4 FIN AF: 0.868

Gnomad4 NFE AF: 0.795

Gnomad4 OTH AF: 0.834

Alfa AF: 0.806 Hom.: 75919

Bravo AF: 0.828

Asia WGS AF: 0.973 AC: 3380 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.56

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: rs4544930; hg19: chr6-128394889;