6-128232071-T-C

Variant names:

• chr6-128232071-T-C
• rs7755473
• NM_002844.4:c.693+7964A>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.693+7964A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.032 in 152,286 control chromosomes in the GnomAD database, including 311 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 0.032 (311 hom., cov: 32)
  • Exomes 𝑓: 0.013 (0 hom.)
• Consequence: PTPRK NM_002844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.684
• Publications: 0 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.293 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.693+7964A>G		intron	N/A	NP_002835.2
	PTPRK	NM_001291981.2		c.693+7964A>G		intron	N/A	NP_001278910.1	Q15262-4
	PTPRK	NM_001135648.3		c.693+7964A>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.693+7964A>G		intron	N/A	ENSP00000357209.4	Q15262-2
	PTPRK	ENST00000532331.5	TSL:1	c.693+7964A>G		intron	N/A	ENSP00000432973.1	Q15262-4
	PTPRK	ENST00000368213.9	TSL:1	c.693+7964A>G		intron	N/A	ENSP00000357196.5	Q15262-3

Frequencies

GnomAD3 genomes AF: 0.0320 AC: 4872 AN: 152092 Hom.: 308 Cov.: 32

Gnomad AFR AF: 0.0371

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0435

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.0253

Gnomad FIN AF: 0.0165

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0103

Gnomad OTH AF: 0.0349

GnomAD4 exome AF: 0.0128 AC: 1 AN: 78 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 66

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 72

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.0320 AC: 4878 AN: 152208 Hom.: 311 Cov.: 32 AF XY: 0.0347 AC XY: 2585 AN XY: 74424

African (AFR) AF: 0.0371 AC: 1541 AN: 41534

American (AMR) AF: 0.0441 AC: 674 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 15 AN: 3472

East Asian (EAS) AF: 0.306 AC: 1574 AN: 5144

South Asian (SAS) AF: 0.0251 AC: 121 AN: 4824

European-Finnish (FIN) AF: 0.0165 AC: 175 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0103 AC: 704 AN: 68020

Other (OTH) AF: 0.0350 AC: 74 AN: 2114

Alfa AF: 0.0214 Hom.: 13

Bravo AF: 0.0349

Asia WGS AF: 0.140 AC: 488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.33
PhyloP100		-0.68
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: rs7755473; hg19: chr6-128553216;