9-9687487-C-T

Variant names:

• chr9-9687487-C-T
• rs4742610
• NM_002839.4:c.-287+47046G>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.-287+47046G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 151,518 control chromosomes in the GnomAD database, including 7,102 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 0.30 (7102 hom., cov: 31)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.421
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRD	NM_002839.4	c.-287+47046G>A		intron_variant	Intron 7 of 45	ENST00000381196.9	NP_002830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRD	ENST00000381196.9	c.-287+47046G>A		intron_variant	Intron 7 of 45	5	NM_002839.4	ENSP00000370593.3
PTPRD	ENST00000463477.5	c.-359+47046G>A		intron_variant	Intron 7 of 16	1		ENSP00000417661.1
PTPRD	ENST00000850942.1	c.-287+47046G>A		intron_variant	Intron 9 of 47			ENSP00000521027.1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45296 AN: 151400 Hom.: 7104 Cov.: 31

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.299 AC: 45300 AN: 151518 Hom.: 7102 Cov.: 31 AF XY: 0.299 AC XY: 22107 AN XY: 74036

African (AFR) AF: 0.255 AC: 10555 AN: 41360

American (AMR) AF: 0.446 AC: 6775 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1321 AN: 3456

East Asian (EAS) AF: 0.333 AC: 1706 AN: 5118

South Asian (SAS) AF: 0.296 AC: 1425 AN: 4808

European-Finnish (FIN) AF: 0.214 AC: 2256 AN: 10536

Middle Eastern (MID) AF: 0.390 AC: 114 AN: 292

European-Non Finnish (NFE) AF: 0.299 AC: 20237 AN: 67766

Other (OTH) AF: 0.347 AC: 727 AN: 2094

Alfa AF: 0.300 Hom.: 29502

Bravo AF: 0.313

Asia WGS AF: 0.300 AC: 1038 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.6
DANN	Benign	0.59
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs4742610; hg19: chr9-9687487;