rs10485686

Positions:

• chr20-42169241-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_007050.6(PTPRT):​c.2492-7699G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 152,106 control chromosomes in the GnomAD database, including 23 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 0.014 (23 hom., cov: 31)
• Consequence: PTPRT NM_007050.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.726

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=-0.91).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.014 (2125/152106) while in subpopulation SAS AF= 0.0366 (176/4804). AF 95% confidence interval is 0.0322. There are 23 homozygotes in gnomad4. There are 946 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2125 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRT	NM_007050.6	c.2492-7699G>A		intron_variant		ENST00000373187.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRT	ENST00000373187.6	c.2492-7699G>A		intron_variant		1	NM_007050.6	P4

Frequencies

GnomAD3 genomes AF: 0.0140 AC: 2131 AN: 151988 Hom.: 23 Cov.: 31

Gnomad AFR AF: 0.00428

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0130

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.00347

Gnomad SAS AF: 0.0370

Gnomad FIN AF: 0.00340

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0199

Gnomad OTH AF: 0.0211

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

GnomAD4 genome AF: 0.0140 AC: 2125 AN: 152106 Hom.: 23 Cov.: 31 AF XY: 0.0127 AC XY: 946 AN XY: 74340

Gnomad4 AFR AF: 0.00427

Gnomad4 AMR AF: 0.0130

Gnomad4 ASJ AF: 0.0144

Gnomad4 EAS AF: 0.00329

Gnomad4 SAS AF: 0.0366

Gnomad4 FIN AF: 0.00340

Gnomad4 NFE AF: 0.0199

Gnomad4 OTH AF: 0.0204

Alfa AF: 0.0138 Hom.: 1

Bravo AF: 0.0132

Asia WGS AF: 0.0210 AC: 75 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.66

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: rs10485686; hg19: chr20-40797881;