rs449090

Variant names:

• chr9-10063345-A-G
• rs449090
• NM_002839.4:c.-544-29555T>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.-544-29555T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,010 control chromosomes in the GnomAD database, including 8,116 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 0.21 (8116 hom., cov: 32)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.573
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRD	NM_002839.4	c.-544-29555T>C		intron_variant	Intron 3 of 45	ENST00000381196.9	NP_002830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRD	ENST00000381196.9	c.-544-29555T>C		intron_variant	Intron 3 of 45	5	NM_002839.4	ENSP00000370593.3
PTPRD	ENST00000463477.5	c.-616-29555T>C		intron_variant	Intron 3 of 16	1		ENSP00000417661.1
PTPRD	ENST00000850942.1	c.-544-29555T>C		intron_variant	Intron 5 of 47			ENSP00000521027.1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31747 AN: 151892 Hom.: 8082 Cov.: 32

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0605

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.0930

Gnomad FIN AF: 0.0267

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0397

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.209 AC: 31835 AN: 152010 Hom.: 8116 Cov.: 32 AF XY: 0.203 AC XY: 15053 AN XY: 74314

African (AFR) AF: 0.611 AC: 25312 AN: 41430

American (AMR) AF: 0.110 AC: 1673 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0605 AC: 210 AN: 3470

East Asian (EAS) AF: 0.143 AC: 737 AN: 5136

South Asian (SAS) AF: 0.0925 AC: 446 AN: 4824

European-Finnish (FIN) AF: 0.0267 AC: 283 AN: 10618

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0397 AC: 2699 AN: 67958

Other (OTH) AF: 0.176 AC: 371 AN: 2108

Alfa AF: 0.152 Hom.: 883

Bravo AF: 0.233

Asia WGS AF: 0.178 AC: 620 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.2
DANN	Benign	0.33
PhyloP100		0.57
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: rs449090; hg19: chr9-10063345;