chr9-10014143-A-G

Variant names:

• chr9-10014143-A-G
• rs1343535
• NM_002839.4:c.-472+19575T>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.-472+19575T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 151,750 control chromosomes in the GnomAD database, including 16,362 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 0.43 (16362 hom., cov: 32)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.483
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002839.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRD	NM_002839.4	MANE Select	c.-472+19575T>C		intron	N/A	NP_002830.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRD	ENST00000381196.9	TSL:5 MANE Select	c.-472+19575T>C		intron	N/A	ENSP00000370593.3
	PTPRD	ENST00000463477.5	TSL:1	c.-544+19575T>C		intron	N/A	ENSP00000417661.1
	PTPRD	ENST00000850942.1		c.-472+19575T>C		intron	N/A	ENSP00000521027.1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64823 AN: 151630 Hom.: 16376 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.469

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

GnomAD4 genome AF: 0.427 AC: 64812 AN: 151750 Hom.: 16362 Cov.: 32 AF XY: 0.430 AC XY: 31850 AN XY: 74148

African (AFR) AF: 0.149 AC: 6183 AN: 41502

American (AMR) AF: 0.436 AC: 6629 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2363 AN: 3462

East Asian (EAS) AF: 0.352 AC: 1817 AN: 5164

South Asian (SAS) AF: 0.576 AC: 2777 AN: 4822

European-Finnish (FIN) AF: 0.548 AC: 5780 AN: 10550

Middle Eastern (MID) AF: 0.610 AC: 177 AN: 290

European-Non Finnish (NFE) AF: 0.556 AC: 37645 AN: 67724

Other (OTH) AF: 0.464 AC: 978 AN: 2106

Alfa AF: 0.387 Hom.: 1887

Bravo AF: 0.407

Asia WGS AF: 0.405 AC: 1408 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.3
DANN	Benign	0.27
PhyloP100		0.48
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: rs1343535; hg19: chr9-10014143; COSMIC: COSV67065630;