20-42079239-C-T

Position:

• chr20-42079239-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_007050.6(PTPRT):​c.*1640G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 208,086 control chromosomes in the GnomAD database, including 4,718 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3317 hom., cov: 33)
  • Exomes 𝑓: 0.21 (1401 hom.)
• Consequence: PTPRT NM_007050.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0670

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]

LOC101927182 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 20-42079239-C-T is Benign according to our data. Variant chr20-42079239-C-T is described in ClinVar as [Benign]. Clinvar id is 1285993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRT	NM_007050.6	c.*1640G>A		3_prime_UTR_variant	31/31	ENST00000373187.6	NP_008981.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRT	ENST00000373187	c.*1640G>A		3_prime_UTR_variant	31/31	1	NM_007050.6	ENSP00000362283.1
PTPRT	ENST00000373193	c.*1640G>A		3_prime_UTR_variant	32/32	1		ENSP00000362289.4

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30517 AN: 152078 Hom.: 3318 Cov.: 33

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.0700

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.210 AC: 11714 AN: 55890 Hom.: 1401 Cov.: 0 AF XY: 0.211 AC XY: 5448 AN XY: 25864

Gnomad4 AFR exome AF: 0.143

Gnomad4 AMR exome AF: 0.157

Gnomad4 ASJ exome AF: 0.261

Gnomad4 EAS exome AF: 0.0628

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.248

Gnomad4 OTH exome AF: 0.224

GnomAD4 genome AF: 0.201 AC: 30518 AN: 152196 Hom.: 3317 Cov.: 33 AF XY: 0.198 AC XY: 14701 AN XY: 74402

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.0696

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.215

Alfa AF: 0.240 Hom.: 4559

Bravo AF: 0.196

Asia WGS AF: 0.107 AC: 374 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 18, 2020	This variant is associated with the following publications: (PMID: 25967969) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.5
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs2866943; hg19: chr20-40707879;