9-10060049-C-T

Variant names:

• chr9-10060049-C-T
• rs419387
• NM_002839.4:c.-544-26259G>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.-544-26259G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 151,894 control chromosomes in the GnomAD database, including 4,653 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 0.17 (4653 hom., cov: 32)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.788
• Publications: 0 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=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRD	NM_002839.4	c.-544-26259G>A		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.-544-26259G>A		intron_variant	Intron 3 of 45	5	NM_002839.4	ENSP00000370593.3
PTPRD	ENST00000463477.5	c.-616-26259G>A		intron_variant	Intron 3 of 16	1		ENSP00000417661.1
PTPRD	ENST00000850942.1	c.-544-26259G>A		intron_variant	Intron 5 of 47			ENSP00000521027.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25065 AN: 151776 Hom.: 4632 Cov.: 32

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0966

Gnomad ASJ AF: 0.0600

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.0930

Gnomad FIN AF: 0.0266

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0393

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.165 AC: 25130 AN: 151894 Hom.: 4653 Cov.: 32 AF XY: 0.161 AC XY: 11945 AN XY: 74220

African (AFR) AF: 0.456 AC: 18911 AN: 41440

American (AMR) AF: 0.0964 AC: 1469 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.0600 AC: 208 AN: 3468

East Asian (EAS) AF: 0.145 AC: 744 AN: 5136

South Asian (SAS) AF: 0.0926 AC: 446 AN: 4814

European-Finnish (FIN) AF: 0.0266 AC: 281 AN: 10582

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0393 AC: 2669 AN: 67900

Other (OTH) AF: 0.143 AC: 301 AN: 2112

Alfa AF: 0.124 Hom.: 748

Bravo AF: 0.183

Asia WGS AF: 0.167 AC: 583 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	14
DANN	Benign	0.83
PhyloP100		0.79
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: rs419387; hg19: chr9-10060049;