9-10454895-C-G

Variant names:

• chr9-10454895-C-G
• rs10511547
• NM_002839.4:c.-599-113878G>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.-599-113878G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0329 in 151,556 control chromosomes in the GnomAD database, including 169 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 0.033 (169 hom., cov: 32)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.113 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.-599-113878G>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.-599-113878G>C		intron	N/A	ENSP00000370593.3
	PTPRD	ENST00000463477.5	TSL:1	c.-671-113878G>C		intron	N/A	ENSP00000417661.1
	PTPRD	ENST00000850942.1		c.-760-113878G>C		intron	N/A	ENSP00000521027.1

Frequencies

GnomAD3 genomes AF: 0.0328 AC: 4969 AN: 151438 Hom.: 167 Cov.: 32

Gnomad AFR AF: 0.0108

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0701

Gnomad ASJ AF: 0.0240

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0541

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0230

Gnomad OTH AF: 0.0365

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

GnomAD4 genome AF: 0.0329 AC: 4980 AN: 151556 Hom.: 169 Cov.: 32 AF XY: 0.0366 AC XY: 2715 AN XY: 74080

African (AFR) AF: 0.0108 AC: 448 AN: 41448

American (AMR) AF: 0.0704 AC: 1070 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.0240 AC: 83 AN: 3456

East Asian (EAS) AF: 0.111 AC: 574 AN: 5164

South Asian (SAS) AF: 0.121 AC: 582 AN: 4820

European-Finnish (FIN) AF: 0.0541 AC: 571 AN: 10552

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0230 AC: 1557 AN: 67616

Other (OTH) AF: 0.0390 AC: 82 AN: 2102

Alfa AF: 0.0253 Hom.: 6

Bravo AF: 0.0323

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
DANN	Benign	0.51
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10511547; hg19: chr9-10454895;