9-9422159-T-C

Variant names:

• chr9-9422159-T-C
• rs4342663
• NM_002839.4:c.-236-24677A>G

Variant summary

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

The NM_002839.4(PTPRD):​c.-236-24677A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 151,904 control chromosomes in the GnomAD database, including 23,777 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 0.56 (23777 hom., cov: 31)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.656
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.608 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.-236-24677A>G		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.-236-24677A>G		intron	N/A	ENSP00000370593.3
	PTPRD	ENST00000463477.5	TSL:1	c.-308-7336A>G		intron	N/A	ENSP00000417661.1
	PTPRD	ENST00000850942.1		c.-236-24677A>G		intron	N/A	ENSP00000521027.1

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84327 AN: 151786 Hom.: 23765 Cov.: 31

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.756

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.555 AC: 84377 AN: 151904 Hom.: 23777 Cov.: 31 AF XY: 0.555 AC XY: 41203 AN XY: 74240

African (AFR) AF: 0.465 AC: 19257 AN: 41438

American (AMR) AF: 0.618 AC: 9418 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 2181 AN: 3472

East Asian (EAS) AF: 0.557 AC: 2867 AN: 5148

South Asian (SAS) AF: 0.453 AC: 2184 AN: 4826

European-Finnish (FIN) AF: 0.594 AC: 6271 AN: 10558

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.591 AC: 40173 AN: 67924

Other (OTH) AF: 0.567 AC: 1193 AN: 2104

Alfa AF: 0.580 Hom.: 69756

Bravo AF: 0.556

Asia WGS AF: 0.510 AC: 1776 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.3
DANN	Benign	0.68
PhyloP100		0.66
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: rs4342663; hg19: chr9-9422159;