6-127972910-C-T

Position:

• chr6-127972910-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.4269+112G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,090,494 control chromosomes in the GnomAD database, including 10,508 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 0.12 (1189 hom., cov: 32)
  • Exomes 𝑓: 0.14 (9319 hom.)
• Consequence: PTPRK NM_002844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.408

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRK	NM_002844.4	c.4269+112G>A		intron_variant		ENST00000368226.9	NP_002835.2
PTPRK	NM_001135648.3	c.4287+112G>A		intron_variant			NP_001129120.1
PTPRK	NM_001291981.2	c.4335+112G>A		intron_variant			NP_001278910.1
PTPRK	NM_001291984.2	c.4266+112G>A		intron_variant			NP_001278913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRK	ENST00000368226.9	c.4269+112G>A		intron_variant		1	NM_002844.4	ENSP00000357209	P4

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18421 AN: 152034 Hom.: 1189 Cov.: 32

Gnomad AFR AF: 0.0975

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.0880

Gnomad ASJ AF: 0.0853

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.104

GnomAD4 exome AF: 0.135 AC: 126778 AN: 938342 Hom.: 9319 AF XY: 0.134 AC XY: 63716 AN XY: 474094

Gnomad4 AFR exome AF: 0.0923

Gnomad4 AMR exome AF: 0.0589

Gnomad4 ASJ exome AF: 0.0972

Gnomad4 EAS exome AF: 0.000733

Gnomad4 SAS exome AF: 0.0983

Gnomad4 FIN exome AF: 0.152

Gnomad4 NFE exome AF: 0.151

Gnomad4 OTH exome AF: 0.124

GnomAD4 genome AF: 0.121 AC: 18422 AN: 152152 Hom.: 1189 Cov.: 32 AF XY: 0.119 AC XY: 8820 AN XY: 74392

Gnomad4 AFR AF: 0.0975

Gnomad4 AMR AF: 0.0878

Gnomad4 ASJ AF: 0.0853

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.103

Alfa AF: 0.132 Hom.: 150

Bravo AF: 0.111

Asia WGS AF: 0.0520 AC: 179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.4
DANN	Benign	0.86

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: rs72975916; hg19: chr6-128294055;