20-42793820-T-G

Variant names:

• chr20-42793820-T-G
• rs10485696
• NM_007050.6:c.215-2354A>C

Variant summary

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

The NM_007050.6(PTPRT):​c.215-2354A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 151,962 control chromosomes in the GnomAD database, including 7,536 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 0.28 (7536 hom., cov: 32)
• Consequence: PTPRT NM_007050.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.862
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRT	NM_007050.6	c.215-2354A>C		intron_variant	Intron 2 of 30	ENST00000373187.6	NP_008981.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRT	ENST00000373187.6	c.215-2354A>C		intron_variant	Intron 2 of 30	1	NM_007050.6	ENSP00000362283.1
PTPRT	ENST00000373193.7	c.215-2354A>C		intron_variant	Intron 2 of 31	1		ENSP00000362289.4
PTPRT	ENST00000617474.1	n.*73-2354A>C		intron_variant	Intron 2 of 30	5		ENSP00000484248.1

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42140 AN: 151844 Hom.: 7536 Cov.: 32

Gnomad AFR AF: 0.0692

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.277 AC: 42130 AN: 151962 Hom.: 7536 Cov.: 32 AF XY: 0.277 AC XY: 20579 AN XY: 74254

African (AFR) AF: 0.0690 AC: 2861 AN: 41486

American (AMR) AF: 0.236 AC: 3609 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 1309 AN: 3468

East Asian (EAS) AF: 0.182 AC: 936 AN: 5130

South Asian (SAS) AF: 0.218 AC: 1045 AN: 4804

European-Finnish (FIN) AF: 0.429 AC: 4523 AN: 10546

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26847 AN: 67940

Other (OTH) AF: 0.282 AC: 596 AN: 2114

Alfa AF: 0.351 Hom.: 28761

Bravo AF: 0.254

Asia WGS AF: 0.195 AC: 681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.91
DANN	Benign	0.46
PhyloP100		-0.86
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: rs10485696; hg19: chr20-41422460;