NM_002839.4:c.5205C>G

Variant names:

• chr9-8340391-G-C
• rs770520673
• NM_002839.4:c.5205C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002839.4(PTPRD):​c.5205C>G​(p.His1735Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PTPRD NM_002839.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35722572).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRD	NM_002839.4	c.5205C>G	p.His1735Gln	missense_variant	Exon 42 of 46	ENST00000381196.9	NP_002830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRD	ENST00000381196.9	c.5205C>G	p.His1735Gln	missense_variant	Exon 42 of 46	5	NM_002839.4	ENSP00000370593.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458798 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725712

African (AFR) AF: 0.00 AC: 0 AN: 33402

American (AMR) AF: 0.00 AC: 0 AN: 44582

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26052

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 85962

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53304

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109858

Other (OTH) AF: 0.00 AC: 0 AN: 60222

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.64	D;.;.;.;.;D;D;.;.
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.081	D
MetaRNN	Benign	0.36	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	-0.010	N;.;.;.;.;N;N;.;.
PhyloP100		1.1
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-5.8	D;D;D;.;D;D;D;D;D
REVEL	Benign	0.20
Sift	Benign	0.069	T;T;T;.;T;T;T;T;T
Sift4G	Benign	0.18	T;T;T;T;T;T;T;T;T
Polyphen		0.66	P;.;.;B;.;P;P;.;.
Vest4		0.38
MutPred		0.40		Gain of MoRF binding (P = 0.0918);.;.;.;.;Gain of MoRF binding (P = 0.0918);Gain of MoRF binding (P = 0.0918);.;.;
MVP		0.48
ClinPred		0.95	D
GERP RS		3.2
Varity_R		0.57
gMVP		0.62
Mutation Taster		=64/36	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs770520673; hg19: chr9-8340391;