rs447578

chr9-10054522-T-C

Variant summary

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

The NM_002839.4(PTPRD):c.-544-20732A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,060 control chromosomes in the GnomAD database, including 2,712 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 0.18 (2712 hom., cov: 32)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRD	NM_002839.4	c.-544-20732A>G		intron_variant		ENST00000381196.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRD	ENST00000381196.9	c.-544-20732A>G		intron_variant		5	NM_002839.4	P1
PTPRD	ENST00000463477.5	c.-616-20732A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26649 AN: 151942 Hom.: 2704 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.0839

Gnomad EAS AF: 0.0151

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.176 AC: 26691 AN: 152060 Hom.: 2712 Cov.: 32 AF XY: 0.173 AC XY: 12821 AN XY: 74324

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.0839

Gnomad4 EAS AF: 0.0147

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.169

Alfa AF: 0.159 Hom.: 278

Bravo AF: 0.184

Asia WGS AF: 0.0900 AC: 314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	2.0
Dann	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs447578; hg19: chr9-10054522;