6-127970054-C-T

Variant names:

• chr6-127970054-C-T
• rs3190930
• NM_002844.4:c.*173G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 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=-0.51).
• 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 rank	MANE	Protein	UniProt
PTPRK	NM_002844.4	c.*173G>A		3_prime_UTR_variant	Exon 30 of 30	ENST00000368226.9	NP_002835.2
PTPRK	NM_001291981.2	c.*173G>A		3_prime_UTR_variant	Exon 33 of 33		NP_001278910.1
PTPRK	NM_001135648.3	c.*173G>A		3_prime_UTR_variant	Exon 31 of 31		NP_001129120.1
PTPRK	NM_001291984.2	c.*173G>A		3_prime_UTR_variant	Exon 30 of 30		NP_001278913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRK	ENST00000368226.9	c.*173G>A		3_prime_UTR_variant	Exon 30 of 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

African (AFR) AF: 0.116 AC: 1026 AN: 8876

American (AMR) AF: 0.185 AC: 1901 AN: 10292

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 2028 AN: 11152

East Asian (EAS) AF: 0.0150 AC: 387 AN: 25786

South Asian (SAS) AF: 0.146 AC: 3342 AN: 22946

European-Finnish (FIN) AF: 0.227 AC: 6123 AN: 26936

Middle Eastern (MID) AF: 0.231 AC: 740 AN: 3204

European-Non Finnish (NFE) AF: 0.234 AC: 49637 AN: 212464

Other (OTH) AF: 0.210 AC: 4396 AN: 20960

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

African (AFR) AF: 0.113 AC: 4707 AN: 41494

American (AMR) AF: 0.195 AC: 2970 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 645 AN: 3462

East Asian (EAS) AF: 0.0158 AC: 82 AN: 5190

South Asian (SAS) AF: 0.144 AC: 695 AN: 4820

European-Finnish (FIN) AF: 0.209 AC: 2198 AN: 10534

Middle Eastern (MID) AF: 0.219 AC: 64 AN: 292

European-Non Finnish (NFE) AF: 0.234 AC: 15918 AN: 67944

Other (OTH) AF: 0.209 AC: 441 AN: 2110

Alfa AF: 0.219 Hom.: 4505

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
PhyloP100		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs3190930; hg19: chr6-128291199;