9-8371609-C-T

Variant names:

• chr9-8371609-C-T
• rs4742490
• NM_002839.4:c.4661+4327G>A

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+4327G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 151,880 control chromosomes in the GnomAD database, including 23,340 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 0.50 (23340 hom., cov: 32)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26
• Publications: 1 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRD	NM_002839.4	c.4661+4327G>A		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+4327G>A		intron_variant	Intron 39 of 45	5	NM_002839.4	ENSP00000370593.3

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76061 AN: 151762 Hom.: 23286 Cov.: 32

Gnomad AFR AF: 0.848

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.502 AC: 76181 AN: 151880 Hom.: 23340 Cov.: 32 AF XY: 0.505 AC XY: 37480 AN XY: 74238

African (AFR) AF: 0.848 AC: 35178 AN: 41466

American (AMR) AF: 0.579 AC: 8831 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1384 AN: 3460

East Asian (EAS) AF: 0.508 AC: 2621 AN: 5160

South Asian (SAS) AF: 0.535 AC: 2575 AN: 4816

European-Finnish (FIN) AF: 0.310 AC: 3274 AN: 10550

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.308 AC: 20930 AN: 67876

Other (OTH) AF: 0.479 AC: 1004 AN: 2098

Alfa AF: 0.361 Hom.: 8248

Bravo AF: 0.535

Asia WGS AF: 0.573 AC: 1991 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.19
DANN	Benign	0.39
PhyloP100		-2.3
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: rs4742490; hg19: chr9-8371609; COSMIC: COSV61934995;