20-42193773-C-T

Variant names:

• chr20-42193773-C-T
• rs979634
• NM_007050.6:c.2491+5467G>A

Variant summary

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

The NM_007050.6(PTPRT):​c.2491+5467G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 152,026 control chromosomes in the GnomAD database, including 25,020 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 0.57 (25020 hom., cov: 32)
• Consequence: PTPRT NM_007050.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRT	NM_007050.6	c.2491+5467G>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.2491+5467G>A		intron_variant	Intron 16 of 30	1	NM_007050.6	ENSP00000362283.1
PTPRT	ENST00000373193.7	c.2557+5467G>A		intron_variant	Intron 17 of 31	1		ENSP00000362289.4
PTPRT	ENST00000617474.1	n.*2358+5467G>A		intron_variant	Intron 16 of 30	5		ENSP00000484248.1

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86613 AN: 151908 Hom.: 25000 Cov.: 32

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.560

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

GnomAD4 genome AF: 0.570 AC: 86677 AN: 152026 Hom.: 25020 Cov.: 32 AF XY: 0.571 AC XY: 42453 AN XY: 74292

African (AFR) AF: 0.604 AC: 25031 AN: 41462

American (AMR) AF: 0.533 AC: 8138 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1922 AN: 3468

East Asian (EAS) AF: 0.391 AC: 2022 AN: 5168

South Asian (SAS) AF: 0.473 AC: 2275 AN: 4808

European-Finnish (FIN) AF: 0.669 AC: 7066 AN: 10568

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

European-Non Finnish (NFE) AF: 0.564 AC: 38340 AN: 67960

Other (OTH) AF: 0.557 AC: 1176 AN: 2112

Alfa AF: 0.471 Hom.: 1968

Bravo AF: 0.561

Asia WGS AF: 0.462 AC: 1607 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	7.9
DANN	Benign	0.27
PhyloP100		1.1
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: rs979634; hg19: chr20-40822413;