6-127972910-C-T

Variant names:

• chr6-127972910-C-T
• rs72975916
• NM_002844.4:c.4269+112G>A

Variant summary

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

The NM_002844.4(PTPRK):​c.4269+112G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,090,494 control chromosomes in the GnomAD database, including 10,508 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 0.12 (1189 hom., cov: 32)
  • Exomes 𝑓: 0.14 (9319 hom.)
• Consequence: PTPRK NM_002844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.408
• Publications: 16 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.148 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.4269+112G>A		intron	N/A	NP_002835.2
	PTPRK	NM_001291981.2		c.4335+112G>A		intron	N/A	NP_001278910.1
	PTPRK	NM_001135648.3		c.4287+112G>A		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.4269+112G>A		intron	N/A	ENSP00000357209.4
	PTPRK	ENST00000532331.5	TSL:1	c.4335+112G>A		intron	N/A	ENSP00000432973.1
	PTPRK	ENST00000368213.9	TSL:1	c.4287+112G>A		intron	N/A	ENSP00000357196.5

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18421 AN: 152034 Hom.: 1189 Cov.: 32

Gnomad AFR AF: 0.0975

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.0880

Gnomad ASJ AF: 0.0853

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.104

GnomAD4 exome AF: 0.135 AC: 126778 AN: 938342 Hom.: 9319 AF XY: 0.134 AC XY: 63716 AN XY: 474094

African (AFR) AF: 0.0923 AC: 2080 AN: 22546

American (AMR) AF: 0.0589 AC: 1850 AN: 31414

Ashkenazi Jewish (ASJ) AF: 0.0972 AC: 1777 AN: 18286

East Asian (EAS) AF: 0.000733 AC: 26 AN: 35478

South Asian (SAS) AF: 0.0983 AC: 5968 AN: 60704

European-Finnish (FIN) AF: 0.152 AC: 6994 AN: 45876

Middle Eastern (MID) AF: 0.108 AC: 491 AN: 4558

European-Non Finnish (NFE) AF: 0.151 AC: 102346 AN: 677146

Other (OTH) AF: 0.124 AC: 5246 AN: 42334

GnomAD4 genome AF: 0.121 AC: 18422 AN: 152152 Hom.: 1189 Cov.: 32 AF XY: 0.119 AC XY: 8820 AN XY: 74392

African (AFR) AF: 0.0975 AC: 4048 AN: 41518

American (AMR) AF: 0.0878 AC: 1342 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0853 AC: 296 AN: 3472

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5184

South Asian (SAS) AF: 0.104 AC: 502 AN: 4824

European-Finnish (FIN) AF: 0.152 AC: 1609 AN: 10584

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10250 AN: 67976

Other (OTH) AF: 0.103 AC: 218 AN: 2110

Alfa AF: 0.131 Hom.: 154

Bravo AF: 0.111

Asia WGS AF: 0.0520 AC: 179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.4
DANN	Benign	0.86
PhyloP100		-0.41
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: rs72975916; hg19: chr6-128294055;