NM_002839.4:c.4386+1340G>T

Variant names:

• chr9-8387892-C-A
• rs1039337
• NM_002839.4:c.4386+1340G>T

Variant summary

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

The NM_002839.4(PTPRD):​c.4386+1340G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,070 control chromosomes in the GnomAD database, including 3,304 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 0.19 (3304 hom., cov: 33)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.710
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRD	NM_002839.4	c.4386+1340G>T		intron_variant	Intron 37 of 45	ENST00000381196.9	NP_002830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRD	ENST00000381196.9	c.4386+1340G>T		intron_variant	Intron 37 of 45	5	NM_002839.4	ENSP00000370593.3

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29084 AN: 151952 Hom.: 3310 Cov.: 33

Gnomad AFR AF: 0.0718

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.191 AC: 29067 AN: 152070 Hom.: 3304 Cov.: 33 AF XY: 0.192 AC XY: 14268 AN XY: 74338

African (AFR) AF: 0.0717 AC: 2974 AN: 41500

American (AMR) AF: 0.201 AC: 3070 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 587 AN: 3470

East Asian (EAS) AF: 0.233 AC: 1201 AN: 5164

South Asian (SAS) AF: 0.155 AC: 749 AN: 4820

European-Finnish (FIN) AF: 0.271 AC: 2860 AN: 10548

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16933 AN: 67978

Other (OTH) AF: 0.200 AC: 423 AN: 2110

Alfa AF: 0.167 Hom.: 1414

Bravo AF: 0.182

Asia WGS AF: 0.165 AC: 575 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.40
DANN	Benign	0.39
PhyloP100		-0.71
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: rs1039337; hg19: chr9-8387892; COSMIC: COSV61959216;