rs6016834

Positions:

• chr20-42581631-A-G
• chr20-42581631-A-T

Variant summary

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

The NM_007050.6(PTPRT):​c.1153+96235T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 152,068 control chromosomes in the GnomAD database, including 11,025 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 0.37 (11025 hom., cov: 32)
• Consequence: PTPRT NM_007050.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.902

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

Verdict is Benign. Variant got -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 = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRT	NM_007050.6	c.1153+96235T>C		intron_variant		ENST00000373187.6	NP_008981.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRT	ENST00000373187.6	c.1153+96235T>C		intron_variant		1	NM_007050.6	ENSP00000362283.1
PTPRT	ENST00000373193.7	c.1153+96235T>C		intron_variant		1		ENSP00000362289.4
PTPRT	ENST00000617474.1	n.*1011+96235T>C		intron_variant		5		ENSP00000484248.1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56958 AN: 151950 Hom.: 11029 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.375 AC: 56966 AN: 152068 Hom.: 11025 Cov.: 32 AF XY: 0.379 AC XY: 28199 AN XY: 74316

Gnomad4 AFR AF: 0.325

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.534

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.459

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.350

Alfa AF: 0.390 Hom.: 11189

Bravo AF: 0.357

Asia WGS AF: 0.411 AC: 1431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.4
DANN	Benign	0.51

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: rs6016834; hg19: chr20-41210271;