9-10139580-T-C

Position:

• chr9-10139580-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRD	NM_002839.4	c.-544-105790A>G		intron_variant		ENST00000381196.9	NP_002830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRD	ENST00000381196.9	c.-544-105790A>G		intron_variant		5	NM_002839.4	ENSP00000370593.3
PTPRD	ENST00000463477.5	c.-616-105790A>G		intron_variant		1		ENSP00000417661.1

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

Gnomad4 AFR AF: 0.611

Gnomad4 AMR AF: 0.768

Gnomad4 ASJ AF: 0.786

Gnomad4 EAS AF: 0.614

Gnomad4 SAS AF: 0.861

Gnomad4 FIN AF: 0.728

Gnomad4 NFE AF: 0.778

Gnomad4 OTH AF: 0.774

Alfa AF: 0.771 Hom.: 43492

Bravo AF: 0.717

Asia WGS AF: 0.749 AC: 2607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.79
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs294845; hg19: chr9-10139580; COSMIC: COSV71789104;