6-128073744-T-C

Variant names:

• chr6-128073744-T-C
• rs4544930
• NM_002844.4:c.1883+5069A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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]

PTPRK-AS1 (HGNC:40484): (PTPRK antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002844.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRK	NM_002844.4	MANE Select	c.1883+5069A>G		intron	N/A	NP_002835.2
	PTPRK	NM_001291981.2		c.1883+5069A>G		intron	N/A	NP_001278910.1	Q15262-4
	PTPRK	NM_001135648.3		c.1883+5069A>G		intron	N/A	NP_001129120.1	Q15262-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRK	ENST00000368226.9	TSL:1 MANE Select	c.1883+5069A>G		intron	N/A	ENSP00000357209.4	Q15262-2
	PTPRK	ENST00000532331.5	TSL:1	c.1883+5069A>G		intron	N/A	ENSP00000432973.1	Q15262-4
	PTPRK	ENST00000368213.9	TSL:1	c.1883+5069A>G		intron	N/A	ENSP00000357196.5	Q15262-3

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

African (AFR) AF: 0.816 AC: 33810 AN: 41442

American (AMR) AF: 0.879 AC: 13375 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.912 AC: 3165 AN: 3472

East Asian (EAS) AF: 0.994 AC: 5141 AN: 5170

South Asian (SAS) AF: 0.974 AC: 4697 AN: 4822

European-Finnish (FIN) AF: 0.868 AC: 9193 AN: 10596

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.795 AC: 54002 AN: 67912

Other (OTH) AF: 0.834 AC: 1759 AN: 2108

Alfa AF: 0.808 Hom.: 128996

Bravo AF: 0.828

Asia WGS AF: 0.973 AC: 3380 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.56
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs4544930; hg19: chr6-128394889;