9-8340356-C-A
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_002839.4(PTPRD):c.5240G>T(p.Arg1747Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,455,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
PTPRD
NM_002839.4 missense
NM_002839.4 missense
Scores
10
6
2
Clinical Significance
Conservation
PhyloP100: 7.91
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.857
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PTPRD | NM_002839.4 | c.5240G>T | p.Arg1747Leu | missense_variant | 42/46 | ENST00000381196.9 | NP_002830.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PTPRD | ENST00000381196.9 | c.5240G>T | p.Arg1747Leu | missense_variant | 42/46 | 5 | NM_002839.4 | ENSP00000370593 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.00000799 AC: 2AN: 250298Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135250
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1455644Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 724016
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GnomAD4 genome Cov.: 33
GnomAD4 genome
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33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 26, 2021 | The c.5240G>T (p.R1747L) alteration is located in exon 42 (coding exon 31) of the PTPRD gene. This alteration results from a G to T substitution at nucleotide position 5240, causing the arginine (R) at amino acid position 1747 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;.;.;.;.;D;D;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
N;.;.;.;.;N;N;.;.
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D;.;D;D;D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D;.;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D;D;D;D
Polyphen
D;.;.;D;.;D;D;.;.
Vest4
MutPred
Loss of MoRF binding (P = 0.0102);.;.;.;.;Loss of MoRF binding (P = 0.0102);Loss of MoRF binding (P = 0.0102);.;.;
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at