chr20-42169241-C-T

Variant names:

• chr20-42169241-C-T
• rs10485686
• NM_007050.6:c.2492-7699G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2125 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRT	NM_007050.6	c.2492-7699G>A		intron_variant	Intron 16 of 30	ENST00000373187.6	NP_008981.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRT	ENST00000373187.6	c.2492-7699G>A		intron_variant	Intron 16 of 30	1	NM_007050.6	ENSP00000362283.1
PTPRT	ENST00000373193.7	c.2558-7699G>A		intron_variant	Intron 17 of 31	1		ENSP00000362289.4
PTPRT	ENST00000617474.1	n.*2359-7699G>A		intron_variant	Intron 16 of 30	5		ENSP00000484248.1

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

African (AFR) AF: 0.00427 AC: 177 AN: 41492

American (AMR) AF: 0.0130 AC: 199 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0144 AC: 50 AN: 3472

East Asian (EAS) AF: 0.00329 AC: 17 AN: 5170

South Asian (SAS) AF: 0.0366 AC: 176 AN: 4804

European-Finnish (FIN) AF: 0.00340 AC: 36 AN: 10594

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0199 AC: 1352 AN: 67976

Other (OTH) AF: 0.0204 AC: 43 AN: 2110

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
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism

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: rs10485686; hg19: chr20-40797881;