rs6065533

Variant names:

• chr20-42766746-C-T
• rs6065533
• NM_007050.6:c.684+4689G>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.684+4689G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,170 control chromosomes in the GnomAD database, including 2,232 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 0.17 (2232 hom., cov: 32)
• Consequence: PTPRT NM_007050.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRT	NM_007050.6	MANE Select	c.684+4689G>A		intron	N/A	NP_008981.4
	PTPRT	NM_001394024.1		c.684+4689G>A		intron	N/A	NP_001380953.1
	PTPRT	NM_133170.4		c.684+4689G>A		intron	N/A	NP_573400.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRT	ENST00000373187.6	TSL:1 MANE Select	c.684+4689G>A		intron	N/A	ENSP00000362283.1
	PTPRT	ENST00000373193.7	TSL:1	c.684+4689G>A		intron	N/A	ENSP00000362289.4
	PTPRT	ENST00000373198.8	TSL:1	c.684+4689G>A		intron	N/A	ENSP00000362294.4

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25320 AN: 152052 Hom.: 2230 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0919

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.166 AC: 25331 AN: 152170 Hom.: 2232 Cov.: 32 AF XY: 0.167 AC XY: 12427 AN XY: 74386

African (AFR) AF: 0.204 AC: 8448 AN: 41504

American (AMR) AF: 0.147 AC: 2253 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 613 AN: 3472

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5182

South Asian (SAS) AF: 0.0922 AC: 444 AN: 4818

European-Finnish (FIN) AF: 0.219 AC: 2314 AN: 10590

Middle Eastern (MID) AF: 0.158 AC: 46 AN: 292

European-Non Finnish (NFE) AF: 0.160 AC: 10867 AN: 67996

Other (OTH) AF: 0.135 AC: 285 AN: 2112

Alfa AF: 0.162 Hom.: 495

Bravo AF: 0.164

Asia WGS AF: 0.0680 AC: 236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.061
DANN	Benign	0.61
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: rs6065533; hg19: chr20-41395386;