rs10976994

Variant names:

• chr9-8361332-C-G
• rs10976994
• NM_002839.4:c.4661+14604G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002839.4(PTPRD):​c.4661+14604G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0663 in 152,148 control chromosomes in the GnomAD database, including 437 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 0.066 (437 hom., cov: 33)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRD	NM_002839.4	c.4661+14604G>C		intron_variant	Intron 39 of 45	ENST00000381196.9	NP_002830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRD	ENST00000381196.9	c.4661+14604G>C		intron_variant	Intron 39 of 45	5	NM_002839.4	ENSP00000370593.3

Frequencies

GnomAD3 genomes AF: 0.0663 AC: 10079 AN: 152030 Hom.: 437 Cov.: 33

Gnomad AFR AF: 0.0242

Gnomad AMI AF: 0.0595

Gnomad AMR AF: 0.0580

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.0391

Gnomad SAS AF: 0.0776

Gnomad FIN AF: 0.0587

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0909

Gnomad OTH AF: 0.0750

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

GnomAD4 genome AF: 0.0663 AC: 10080 AN: 152148 Hom.: 437 Cov.: 33 AF XY: 0.0642 AC XY: 4773 AN XY: 74364

African (AFR) AF: 0.0241 AC: 1002 AN: 41528

American (AMR) AF: 0.0579 AC: 885 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 567 AN: 3466

East Asian (EAS) AF: 0.0392 AC: 203 AN: 5176

South Asian (SAS) AF: 0.0779 AC: 375 AN: 4814

European-Finnish (FIN) AF: 0.0587 AC: 621 AN: 10576

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0910 AC: 6184 AN: 67990

Other (OTH) AF: 0.0743 AC: 157 AN: 2114

Alfa AF: 0.0747 Hom.: 62

Bravo AF: 0.0645

Asia WGS AF: 0.0680 AC: 239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
DANN	Benign	0.60
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10976994; hg19: chr9-8361332;