20-42365454-T-C

Variant summary

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

The NM_007050.6(PTPRT):c.1561-13169A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 151,886 control chromosomes in the GnomAD database, including 12,067 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 0.39 (12067 hom., cov: 30)
• Consequence: PTPRT NM_007050.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.549

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRT	NM_007050.6	c.1561-13169A>G		intron_variant		ENST00000373187.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRT	ENST00000373187.6	c.1561-13169A>G		intron_variant		1	NM_007050.6	P4

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59248 AN: 151768 Hom.: 12047 Cov.: 30

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.391 AC: 59324 AN: 151886 Hom.: 12067 Cov.: 30 AF XY: 0.391 AC XY: 29028 AN XY: 74228

Gnomad4 AFR AF: 0.468

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.634

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.392

Alfa AF: 0.351 Hom.: 5489

Bravo AF: 0.402

Asia WGS AF: 0.551 AC: 1913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.62
Dann	Benign	0.51

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: rs6030171; hg19: chr20-40994094;