rs6065533

Positions:

• chr20-42766746-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007050.6(PTPRT):​c.684+4689G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,170 control chromosomes in the GnomAD database, including 2,232 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 0.17 (2232 hom., cov: 32)
• Consequence: PTPRT NM_007050.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

Genes affected

PTPRT (HGNC:9682): (protein tyrosine phosphatase receptor type T) 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 intracellular catalytic domains, and thus represents a receptor-type PTP. The extracellular region contains a meprin-A5 antigen-PTP (MAM) domain, Ig-like and fibronectin type III-like repeats. The protein domain structure and the expression pattern of the mouse counterpart of this PTP suggest its roles in both signal transduction and cellular adhesion in the central nervous system. Two alternatively spliced transcript variants of this gene, which encode distinct proteins, have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRT	NM_007050.6	c.684+4689G>A		intron_variant		ENST00000373187.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRT	ENST00000373187.6	c.684+4689G>A		intron_variant		1	NM_007050.6	P4

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25320 AN: 152052 Hom.: 2230 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0919

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.166 AC: 25331 AN: 152170 Hom.: 2232 Cov.: 32 AF XY: 0.167 AC XY: 12427 AN XY: 74386

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.0922

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.135

Alfa AF: 0.159 Hom.: 403

Bravo AF: 0.164

Asia WGS AF: 0.0680 AC: 236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.061
DANN	Benign	0.61

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: rs6065533; hg19: chr20-41395386;