9-9503477-T-C

Variant names:

• chr9-9503477-T-C
• rs1332199
• NM_002839.4:c.-237+71255A>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.-237+71255A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.872 in 151,380 control chromosomes in the GnomAD database, including 57,864 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 0.87 (57864 hom., cov: 29)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRD	NM_002839.4	c.-237+71255A>G		intron_variant	Intron 8 of 45	ENST00000381196.9	NP_002830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRD	ENST00000381196.9	c.-237+71255A>G		intron_variant	Intron 8 of 45	5	NM_002839.4	ENSP00000370593.3
PTPRD	ENST00000463477.5	c.-309+71255A>G		intron_variant	Intron 8 of 16	1		ENSP00000417661.1
PTPRD	ENST00000850942.1	c.-237+71255A>G		intron_variant	Intron 10 of 47			ENSP00000521027.1

Frequencies

GnomAD3 genomes AF: 0.872 AC: 131859 AN: 151262 Hom.: 57807 Cov.: 29

Gnomad AFR AF: 0.969

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.893

Gnomad EAS AF: 0.845

Gnomad SAS AF: 0.897

Gnomad FIN AF: 0.813

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.822

Gnomad OTH AF: 0.880

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

GnomAD4 genome AF: 0.872 AC: 131974 AN: 151380 Hom.: 57864 Cov.: 29 AF XY: 0.871 AC XY: 64428 AN XY: 73938

African (AFR) AF: 0.969 AC: 40082 AN: 41366

American (AMR) AF: 0.868 AC: 13132 AN: 15132

Ashkenazi Jewish (ASJ) AF: 0.893 AC: 3089 AN: 3460

East Asian (EAS) AF: 0.844 AC: 4306 AN: 5102

South Asian (SAS) AF: 0.897 AC: 4314 AN: 4810

European-Finnish (FIN) AF: 0.813 AC: 8573 AN: 10548

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.822 AC: 55633 AN: 67658

Other (OTH) AF: 0.878 AC: 1845 AN: 2102

Alfa AF: 0.842 Hom.: 61532

Bravo AF: 0.881

Asia WGS AF: 0.862 AC: 2999 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.74
DANN	Benign	0.55
PhyloP100		-0.052
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: rs1332199; hg19: chr9-9503477; COSMIC: COSV67053049;