rs761011

Positions:

• chr20-42687851-G-A
• chr20-42687851-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007050.6(PTPRT):​c.860-9692C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,164 control chromosomes in the GnomAD database, including 2,226 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 0.14 (2226 hom., cov: 32)
  • Exomes 𝑓: 0.33 (0 hom.)
• Consequence: PTPRT NM_007050.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.143

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRT	NM_007050.6	c.860-9692C>T		intron_variant		ENST00000373187.6	NP_008981.4
LOC101927159	NR_110004.1	n.1284G>A		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRT	ENST00000373187.6	c.860-9692C>T		intron_variant		1	NM_007050.6	ENSP00000362283	P4
	ENST00000457704.2	n.1284G>A		non_coding_transcript_exon_variant	4/4	1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21698 AN: 152040 Hom.: 2212 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.0931

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.0300

Gnomad FIN AF: 0.0973

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0908

Gnomad OTH AF: 0.121

GnomAD4 exome AF: 0.333 AC: 2 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

Gnomad4 NFE exome AF: 0.333

GnomAD4 genome AF: 0.143 AC: 21744 AN: 152158 Hom.: 2226 Cov.: 32 AF XY: 0.138 AC XY: 10254 AN XY: 74382

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.0931

Gnomad4 EAS AF: 0.00347

Gnomad4 SAS AF: 0.0305

Gnomad4 FIN AF: 0.0973

Gnomad4 NFE AF: 0.0908

Gnomad4 OTH AF: 0.119

Alfa AF: 0.0963 Hom.: 1703

Bravo AF: 0.154

Asia WGS AF: 0.0370 AC: 129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.6
DANN	Benign	0.59

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: rs761011; hg19: chr20-41316491;