chr20-42774267-A-G

Variant names:

• chr20-42774267-A-G
• rs1885831
• NM_007050.6:c.569-2717T>C

Variant summary

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

The NM_007050.6(PTPRT):​c.569-2717T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,146 control chromosomes in the GnomAD database, including 2,237 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 0.16 (2237 hom., cov: 33)
• Consequence: PTPRT NM_007050.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 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.569-2717T>C		intron	N/A	NP_008981.4
	PTPRT	NM_001394024.1		c.569-2717T>C		intron	N/A	NP_001380953.1
	PTPRT	NM_133170.4		c.569-2717T>C		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.569-2717T>C		intron	N/A	ENSP00000362283.1
	PTPRT	ENST00000373193.7	TSL:1	c.569-2717T>C		intron	N/A	ENSP00000362289.4
	PTPRT	ENST00000373198.8	TSL:1	c.569-2717T>C		intron	N/A	ENSP00000362294.4

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24495 AN: 152026 Hom.: 2232 Cov.: 33

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.161 AC: 24502 AN: 152146 Hom.: 2237 Cov.: 33 AF XY: 0.163 AC XY: 12093 AN XY: 74382

African (AFR) AF: 0.124 AC: 5148 AN: 41526

American (AMR) AF: 0.198 AC: 3021 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 582 AN: 3470

East Asian (EAS) AF: 0.394 AC: 2029 AN: 5156

South Asian (SAS) AF: 0.198 AC: 956 AN: 4822

European-Finnish (FIN) AF: 0.142 AC: 1509 AN: 10600

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10621 AN: 67978

Other (OTH) AF: 0.184 AC: 388 AN: 2108

Alfa AF: 0.159 Hom.: 3353

Bravo AF: 0.162

Asia WGS AF: 0.280 AC: 975 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.64
PhyloP100		-0.17
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: rs1885831; hg19: chr20-41402907; COSMIC: COSV62012445;