20-42331566-C-T

Variant names:

• chr20-42331566-C-T
• rs2227158
• NM_007050.6:c.1866-15570G>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.1866-15570G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,944 control chromosomes in the GnomAD database, including 14,042 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 0.40 (14042 hom., cov: 33)
• Consequence: PTPRT NM_007050.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.966
• 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=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007050.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRT	NM_007050.6	MANE Select	c.1866-15570G>A		intron	N/A	NP_008981.4
	PTPRT	NM_001394024.1		c.1866-15570G>A		intron	N/A	NP_001380953.1
	PTPRT	NM_133170.4		c.1866-15570G>A		intron	N/A	NP_573400.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRT	ENST00000373187.6	TSL:1 MANE Select	c.1866-15570G>A		intron	N/A	ENSP00000362283.1	O14522-3
	PTPRT	ENST00000373193.7	TSL:1	c.1866-15570G>A		intron	N/A	ENSP00000362289.4	O14522-1
	PTPRT	ENST00000373198.8	TSL:1	c.1866-15570G>A		intron	N/A	ENSP00000362294.4	A0A075B6H0

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61298 AN: 151826 Hom.: 14039 Cov.: 33

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.404 AC: 61325 AN: 151944 Hom.: 14042 Cov.: 33 AF XY: 0.405 AC XY: 30087 AN XY: 74272

African (AFR) AF: 0.169 AC: 6982 AN: 41424

American (AMR) AF: 0.492 AC: 7508 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1665 AN: 3470

East Asian (EAS) AF: 0.588 AC: 3037 AN: 5164

South Asian (SAS) AF: 0.462 AC: 2225 AN: 4816

European-Finnish (FIN) AF: 0.476 AC: 5015 AN: 10542

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33713 AN: 67942

Other (OTH) AF: 0.400 AC: 845 AN: 2112

Alfa AF: 0.466 Hom.: 27720

Bravo AF: 0.395

Asia WGS AF: 0.507 AC: 1766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	7.7
DANN	Benign	0.72
PhyloP100		0.97
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: rs2227158; hg19: chr20-40960206;