rs419387

Positions:

• chr9-10060049-C-T

Variant summary

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

The NM_002839.4(PTPRD):​c.-544-26259G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 151,894 control chromosomes in the GnomAD database, including 4,653 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 (4653 hom., cov: 32)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.788

Genes affected

PTPRD (HGNC:9668): (protein tyrosine phosphatase receptor type D) 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 contains an extracellular region, a single transmembrane segment and two tandem intracytoplasmic catalytic domains, and thus represents a receptor-type PTP. The extracellular region of this protein is composed of three Ig-like and eight fibronectin type III-like domains. Studies of the similar genes in chicken and fly suggest the role of this PTP is in promoting neurite growth, and regulating neurons axon guidance. Multiple alternatively spliced transcript variants of this gene have been reported. A related pseudogene has been identified on chromosome 5. [provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) 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
PTPRD	NM_002839.4	c.-544-26259G>A		intron_variant		ENST00000381196.9	NP_002830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRD	ENST00000381196.9	c.-544-26259G>A		intron_variant		5	NM_002839.4	ENSP00000370593	P1
PTPRD	ENST00000463477.5	c.-616-26259G>A		intron_variant		1		ENSP00000417661

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25065 AN: 151776 Hom.: 4632 Cov.: 32

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0966

Gnomad ASJ AF: 0.0600

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.0930

Gnomad FIN AF: 0.0266

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0393

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.165 AC: 25130 AN: 151894 Hom.: 4653 Cov.: 32 AF XY: 0.161 AC XY: 11945 AN XY: 74220

Gnomad4 AFR AF: 0.456

Gnomad4 AMR AF: 0.0964

Gnomad4 ASJ AF: 0.0600

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.0926

Gnomad4 FIN AF: 0.0266

Gnomad4 NFE AF: 0.0393

Gnomad4 OTH AF: 0.143

Alfa AF: 0.103 Hom.: 545

Bravo AF: 0.183

Asia WGS AF: 0.167 AC: 583 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	14
DANN	Benign	0.83

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs419387; hg19: chr9-10060049;