rs10977260

Positions:

• chr9-8720393-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.64+13387A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0579 in 152,224 control chromosomes in the GnomAD database, including 383 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 0.058 (383 hom., cov: 32)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.279

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRD	NM_002839.4	c.64+13387A>G		intron_variant		ENST00000381196.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRD	ENST00000381196.9	c.64+13387A>G		intron_variant		5	NM_002839.4	P1

Frequencies

GnomAD3 genomes AF: 0.0580 AC: 8818 AN: 152108 Hom.: 382 Cov.: 32

Gnomad AFR AF: 0.0141

Gnomad AMI AF: 0.0626

Gnomad AMR AF: 0.0346

Gnomad ASJ AF: 0.0726

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0373

Gnomad FIN AF: 0.0647

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0940

Gnomad OTH AF: 0.0581

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

GnomAD4 genome AF: 0.0579 AC: 8818 AN: 152224 Hom.: 383 Cov.: 32 AF XY: 0.0550 AC XY: 4096 AN XY: 74432

Gnomad4 AFR AF: 0.0140

Gnomad4 AMR AF: 0.0346

Gnomad4 ASJ AF: 0.0726

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0376

Gnomad4 FIN AF: 0.0647

Gnomad4 NFE AF: 0.0940

Gnomad4 OTH AF: 0.0570

Alfa AF: 0.0862 Hom.: 856

Bravo AF: 0.0544

Asia WGS AF: 0.0200 AC: 70 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.61

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: rs10977260; hg19: chr9-8720393;