rs754548492

Variant names:

• chr6-127985772-C-T
• rs754548492
• NM_002844.4:c.3200G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-127985772-C-T
• chr6-127985772-C-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_002844.4(PTPRK):​c.3200G>A​(p.Arg1067Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,613,748 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: PTPRK NM_002844.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91
• Publications: 2 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 31 AD gene.

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.3200G>A	p.Arg1067Gln	missense	Exon 22 of 30	NP_002835.2
	PTPRK	NM_001291981.2		c.3266G>A	p.Arg1089Gln	missense	Exon 25 of 33	NP_001278910.1	Q15262-4
	PTPRK	NM_001135648.3		c.3218G>A	p.Arg1073Gln	missense	Exon 23 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.3200G>A	p.Arg1067Gln	missense	Exon 22 of 30	ENSP00000357209.4	Q15262-2
	PTPRK	ENST00000532331.5	TSL:1	c.3266G>A	p.Arg1089Gln	missense	Exon 25 of 33	ENSP00000432973.1	Q15262-4
	PTPRK	ENST00000368213.9	TSL:1	c.3218G>A	p.Arg1073Gln	missense	Exon 23 of 31	ENSP00000357196.5	Q15262-3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152126 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000478 AC: 12 AN: 251286 AF XY: 0.0000442

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000212 AC: 31 AN: 1461622 Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11 AN XY: 727110

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.000157 AC: 7 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39686

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86240

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1111836

Other (OTH) AF: 0.0000166 AC: 1 AN: 60378

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152126 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74302

African (AFR) AF: 0.00 AC: 0 AN: 41426

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000741 AC: 9

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Pathogenic	0.25
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.24	T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Uncertain	-0.049	T
MutationAssessor	Benign	1.1	L
PhyloP100		7.9
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.49	N
REVEL	Pathogenic	0.65
Sift	Benign	0.41	T
Sift4G	Benign	0.55	T
Polyphen		1.0	D
Vest4		0.90
MutPred		0.62		Gain of methylation at K1068 (P = 0.1122)
MVP		0.56
MPC		1.4
ClinPred		0.36	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.55
Mutation Taster		=27/73	disease causing

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: rs754548492; hg19: chr6-128306917;