9-10139580-T-C

Variant names:

• chr9-10139580-T-C
• rs294845
• NM_002839.4:c.-544-105790A>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.-544-105790A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 151,928 control chromosomes in the GnomAD database, including 40,546 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 0.73 (40546 hom., cov: 31)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19
• Publications: 10 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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.839 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRD	NM_002839.4	MANE Select	c.-544-105790A>G		intron	N/A	NP_002830.1	P23468-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRD	ENST00000381196.9	TSL:5 MANE Select	c.-544-105790A>G		intron	N/A	ENSP00000370593.3	P23468-1
	PTPRD	ENST00000463477.5	TSL:1	c.-616-105790A>G		intron	N/A	ENSP00000417661.1	C9J8S8
	PTPRD	ENST00000850942.1		c.-633-37252A>G		intron	N/A	ENSP00000521027.1

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110192 AN: 151810 Hom.: 40519 Cov.: 31

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.863

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.786

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.860

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.773

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

GnomAD4 genome AF: 0.726 AC: 110268 AN: 151928 Hom.: 40546 Cov.: 31 AF XY: 0.729 AC XY: 54148 AN XY: 74252

African (AFR) AF: 0.611 AC: 25333 AN: 41450

American (AMR) AF: 0.768 AC: 11686 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.786 AC: 2725 AN: 3468

East Asian (EAS) AF: 0.614 AC: 3162 AN: 5146

South Asian (SAS) AF: 0.861 AC: 4150 AN: 4822

European-Finnish (FIN) AF: 0.728 AC: 7696 AN: 10570

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.778 AC: 52836 AN: 67940

Other (OTH) AF: 0.774 AC: 1637 AN: 2114

Alfa AF: 0.757 Hom.: 114970

Bravo AF: 0.717

Asia WGS AF: 0.749 AC: 2607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.79
DANN	Benign	0.44
PhyloP100		-2.2
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: rs294845; hg19: chr9-10139580; COSMIC: COSV71789104;