20-42254063-T-C

Variant names:

• chr20-42254063-T-C
• rs6030089
• NM_007050.6:c.2177-5241A>G

Variant summary

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

The NM_007050.6(PTPRT):​c.2177-5241A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 152,000 control chromosomes in the GnomAD database, including 19,047 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 0.47 (19047 hom., cov: 31)
• Consequence: PTPRT NM_007050.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0750
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRT	NM_007050.6	c.2177-5241A>G		intron_variant	Intron 13 of 30	ENST00000373187.6	NP_008981.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRT	ENST00000373187.6	c.2177-5241A>G		intron_variant	Intron 13 of 30	1	NM_007050.6	ENSP00000362283.1
PTPRT	ENST00000373193.7	c.2234-5241A>G		intron_variant	Intron 14 of 31	1		ENSP00000362289.4
PTPRT	ENST00000617474.1	n.*2035-5241A>G		intron_variant	Intron 13 of 30	5		ENSP00000484248.1

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72187 AN: 151884 Hom.: 19057 Cov.: 31

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.475 AC: 72187 AN: 152000 Hom.: 19047 Cov.: 31 AF XY: 0.479 AC XY: 35593 AN XY: 74282

African (AFR) AF: 0.233 AC: 9667 AN: 41468

American (AMR) AF: 0.510 AC: 7785 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1925 AN: 3472

East Asian (EAS) AF: 0.430 AC: 2212 AN: 5150

South Asian (SAS) AF: 0.493 AC: 2366 AN: 4804

European-Finnish (FIN) AF: 0.672 AC: 7103 AN: 10572

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39300 AN: 67944

Other (OTH) AF: 0.503 AC: 1062 AN: 2112

Alfa AF: 0.403 Hom.: 1277

Bravo AF: 0.452

Asia WGS AF: 0.452 AC: 1576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.56
PhyloP100		-0.075
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: rs6030089; hg19: chr20-40882703;