9-8879118-C-T

Variant names:

• chr9-8879118-C-T
• rs17584499
• NM_002839.4:c.-104+139579G>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.-104+139579G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,130 control chromosomes in the GnomAD database, including 1,995 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 0.15 (1995 hom., cov: 32)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.635
• Publications: 118 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRD	NM_002839.4	c.-104+139579G>A		intron_variant	Intron 11 of 45	ENST00000381196.9	NP_002830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRD	ENST00000381196.9	c.-104+139579G>A		intron_variant	Intron 11 of 45	5	NM_002839.4	ENSP00000370593.3
PTPRD	ENST00000463477.5	c.-104+139579G>A		intron_variant	Intron 12 of 16	1		ENSP00000417661.1
PTPRD	ENST00000850942.1	c.-104+139579G>A		intron_variant	Intron 13 of 47			ENSP00000521027.1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22498 AN: 152012 Hom.: 1997 Cov.: 32

Gnomad AFR AF: 0.0545

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.148 AC: 22504 AN: 152130 Hom.: 1995 Cov.: 32 AF XY: 0.147 AC XY: 10959 AN XY: 74364

African (AFR) AF: 0.0545 AC: 2264 AN: 41506

American (AMR) AF: 0.204 AC: 3126 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 529 AN: 3472

East Asian (EAS) AF: 0.120 AC: 621 AN: 5158

South Asian (SAS) AF: 0.259 AC: 1248 AN: 4810

European-Finnish (FIN) AF: 0.133 AC: 1407 AN: 10582

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12850 AN: 67990

Other (OTH) AF: 0.154 AC: 325 AN: 2116

Alfa AF: 0.177 Hom.: 10852

Bravo AF: 0.146

Asia WGS AF: 0.185 AC: 643 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.6
DANN	Benign	0.77
PhyloP100		0.64
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: rs17584499; hg19: chr9-8879118;