rs639168

Positions:

• chr9-9539574-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.-237+35158G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 151,702 control chromosomes in the GnomAD database, including 2,071 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 (2071 hom., cov: 32)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.257

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRD	NM_002839.4	c.-237+35158G>A		intron_variant		ENST00000381196.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRD	ENST00000381196.9	c.-237+35158G>A		intron_variant		5	NM_002839.4	P1
PTPRD	ENST00000463477.5	c.-309+35158G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24114 AN: 151582 Hom.: 2061 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.0835

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.159 AC: 24167 AN: 151702 Hom.: 2071 Cov.: 32 AF XY: 0.159 AC XY: 11766 AN XY: 74166

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.0840

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.132

Alfa AF: 0.149 Hom.: 371

Bravo AF: 0.161

Asia WGS AF: 0.155 AC: 540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.3
DANN	Benign	0.64

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: rs639168; hg19: chr9-9539574; COSMIC: COSV67006046;