6-127970054-C-T

Position:

• chr6-127970054-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.*173G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 494,634 control chromosomes in the GnomAD database, including 10,922 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 (2923 hom., cov: 32)
  • Exomes 𝑓: 0.20 (7999 hom.)
• Consequence: PTPRK NM_002844.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45

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=-0.51).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRK	NM_002844.4	c.*173G>A		3_prime_UTR_variant	30/30	ENST00000368226.9	NP_002835.2
PTPRK	NM_001291981.2	c.*173G>A		3_prime_UTR_variant	33/33		NP_001278910.1
PTPRK	NM_001135648.3	c.*173G>A		3_prime_UTR_variant	31/31		NP_001129120.1
PTPRK	NM_001291984.2	c.*173G>A		3_prime_UTR_variant	30/30		NP_001278913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRK	ENST00000368226	c.*173G>A		3_prime_UTR_variant	30/30	1	NM_002844.4	ENSP00000357209.4

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27830 AN: 151900 Hom.: 2923 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0158

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.213

GnomAD4 exome AF: 0.203 AC: 69580 AN: 342616 Hom.: 7999 Cov.: 4 AF XY: 0.201 AC XY: 36057 AN XY: 179128

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.185

Gnomad4 ASJ exome AF: 0.182

Gnomad4 EAS exome AF: 0.0150

Gnomad4 SAS exome AF: 0.146

Gnomad4 FIN exome AF: 0.227

Gnomad4 NFE exome AF: 0.234

Gnomad4 OTH exome AF: 0.210

GnomAD4 genome AF: 0.183 AC: 27828 AN: 152018 Hom.: 2923 Cov.: 32 AF XY: 0.182 AC XY: 13492 AN XY: 74330

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.0158

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.209

Alfa AF: 0.219 Hom.: 3808

Bravo AF: 0.184

Asia WGS AF: 0.0890 AC: 309 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	14
DANN	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs3190930; hg19: chr6-128291199;