6-127983668-T-G

Variant names:

• chr6-127983668-T-G
• rs9402010
• NM_002844.4:c.3252-291A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002844.4(PTPRK):​c.3252-291A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0876 in 152,252 control chromosomes in the GnomAD database, including 774 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 0.088 (774 hom., cov: 32)
• Consequence: PTPRK NM_002844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.158
• Publications: 3 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRK	NM_002844.4	MANE Select	c.3252-291A>C		intron	N/A	NP_002835.2
	PTPRK	NM_001291981.2		c.3318-291A>C		intron	N/A	NP_001278910.1
	PTPRK	NM_001135648.3		c.3270-291A>C		intron	N/A	NP_001129120.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRK	ENST00000368226.9	TSL:1 MANE Select	c.3252-291A>C		intron	N/A	ENSP00000357209.4
	PTPRK	ENST00000532331.5	TSL:1	c.3318-291A>C		intron	N/A	ENSP00000432973.1
	PTPRK	ENST00000368213.9	TSL:1	c.3270-291A>C		intron	N/A	ENSP00000357196.5

Frequencies

GnomAD3 genomes AF: 0.0877 AC: 13339 AN: 152134 Hom.: 772 Cov.: 32

Gnomad AFR AF: 0.0560

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0678

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0556

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0964

Gnomad OTH AF: 0.0943

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

GnomAD4 genome AF: 0.0876 AC: 13337 AN: 152252 Hom.: 774 Cov.: 32 AF XY: 0.0859 AC XY: 6396 AN XY: 74444

African (AFR) AF: 0.0560 AC: 2327 AN: 41552

American (AMR) AF: 0.0677 AC: 1035 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 536 AN: 3468

East Asian (EAS) AF: 0.290 AC: 1504 AN: 5178

South Asian (SAS) AF: 0.110 AC: 532 AN: 4830

European-Finnish (FIN) AF: 0.0556 AC: 590 AN: 10618

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0964 AC: 6556 AN: 67998

Other (OTH) AF: 0.0928 AC: 196 AN: 2112

Alfa AF: 0.0890 Hom.: 209

Bravo AF: 0.0893

Asia WGS AF: 0.170 AC: 593 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.4
DANN	Benign	0.82
PhyloP100		0.16
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: rs9402010; hg19: chr6-128304813; COSMIC: COSV63905710; COSMIC: COSV63905710;