rs9491896

chr6-127979804-G-Achr6-127979804-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002844.4(PTPRK):c.3711+1312C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0885 in 152,278 control chromosomes in the GnomAD database, including 777 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 0.089 (777 hom., cov: 33)
• Consequence: PTPRK NM_002844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRK	NM_002844.4	c.3711+1312C>T		intron_variant		ENST00000368226.9
PTPRK	NM_001135648.3	c.3729+1312C>T		intron_variant
PTPRK	NM_001291981.2	c.3777+1312C>T		intron_variant
PTPRK	NM_001291984.2	c.3708+1312C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRK	ENST00000368226.9	c.3711+1312C>T		intron_variant		1	NM_002844.4	P4

Frequencies

GnomAD3 genomes AF: 0.0886 AC: 13485 AN: 152160 Hom.: 775 Cov.: 33

Gnomad AFR AF: 0.0560

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0688

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0553

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0991

Gnomad OTH AF: 0.0948

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0885 AC: 13484 AN: 152278 Hom.: 777 Cov.: 33 AF XY: 0.0866 AC XY: 6448 AN XY: 74468

Gnomad4 AFR AF: 0.0560

Gnomad4 AMR AF: 0.0687

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.282

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.0553

Gnomad4 NFE AF: 0.0991

Gnomad4 OTH AF: 0.0934

Alfa AF: 0.0983 Hom.: 1390

Bravo AF: 0.0902

Asia WGS AF: 0.166 AC: 577 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.37
Dann	Benign	0.21

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: rs9491896; hg19: chr6-128300949; COSMIC: COSV63905708;