rs35140919

Variant names:

• chr6-127981272-G-A
• rs35140919
• NM_002844.4:c.3555C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-127981272-G-A
• chr6-127981272-G-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_002844.4(PTPRK):​c.3555C>T​(p.Thr1185Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T1185T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTPRK NM_002844.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57

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 Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP7: Synonymous conserved (PhyloP=1.57 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRK	NM_002844.4	c.3555C>T	p.Thr1185Thr	synonymous_variant	Exon 25 of 30	ENST00000368226.9	NP_002835.2
PTPRK	NM_001291981.2	c.3621C>T	p.Thr1207Thr	synonymous_variant	Exon 28 of 33		NP_001278910.1
PTPRK	NM_001135648.3	c.3573C>T	p.Thr1191Thr	synonymous_variant	Exon 26 of 31		NP_001129120.1
PTPRK	NM_001291984.2	c.3552C>T	p.Thr1184Thr	synonymous_variant	Exon 25 of 30		NP_001278913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRK	ENST00000368226.9	c.3555C>T	p.Thr1185Thr	synonymous_variant	Exon 25 of 30	1	NM_002844.4	ENSP00000357209.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	8.5
DANN	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs35140919; hg19: chr6-128302417;