NM_002844.4:c.1796A>T

Variant names:

• chr6-128078900-T-A
• rs1482980901
• NM_002844.4:c.1796A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002844.4(PTPRK):​c.1796A>T​(p.Tyr599Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,459,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y599C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PTPRK NM_002844.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.05
• 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]

PTPRK-AS1 (HGNC:40484): (PTPRK antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41610283).

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.1796A>T	p.Tyr599Phe	missense	Exon 11 of 30	NP_002835.2
	PTPRK	NM_001291981.2		c.1796A>T	p.Tyr599Phe	missense	Exon 11 of 33	NP_001278910.1	Q15262-4
	PTPRK	NM_001135648.3		c.1796A>T	p.Tyr599Phe	missense	Exon 11 of 31	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.1796A>T	p.Tyr599Phe	missense	Exon 11 of 30	ENSP00000357209.4	Q15262-2
	PTPRK	ENST00000532331.5	TSL:1	c.1796A>T	p.Tyr599Phe	missense	Exon 11 of 33	ENSP00000432973.1	Q15262-4
	PTPRK	ENST00000368213.9	TSL:1	c.1796A>T	p.Tyr599Phe	missense	Exon 11 of 31	ENSP00000357196.5	Q15262-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459038 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725910

African (AFR) AF: 0.0000300 AC: 1 AN: 33362

American (AMR) AF: 0.00 AC: 0 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26034

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.00 AC: 0 AN: 86162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109776

Other (OTH) AF: 0.00 AC: 0 AN: 60268

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.0026	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.080	T
Eigen	Uncertain	0.64
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		6.1
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.017	D
Polyphen		0.89	P
Vest4		0.52
MutPred		0.34		Loss of phosphorylation at Y599 (P = 0.0187)
MVP		0.49
MPC		1.1
ClinPred		0.96	D
GERP RS		5.9
Varity_R		0.58
gMVP		0.51
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1482980901; hg19: chr6-128400045;