rs775633137
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP5BS2
The NM_001191057.4(PDE1C):c.778G>T(p.Ala260Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,612,918 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (no stars).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
PDE1C
NM_001191057.4 missense
NM_001191057.4 missense
Scores
3
11
4
Clinical Significance
Conservation
PhyloP100: 6.00
Genes affected
PDE1C (HGNC:8776): (phosphodiesterase 1C) This gene encodes an enzyme that belongs to the 3'5'-cyclic nucleotide phosphodiesterase family. Members of this family catalyze hydrolysis of the cyclic nucleotides, cyclic adenosine monophosphate and cyclic guanosine monophosphate, to the corresponding nucleoside 5'-monophosphates. The enzyme encoded by this gene regulates proliferation and migration of vascular smooth muscle cells, and neointimal hyperplasia. This enzyme also plays a role in pathological vascular remodeling by regulating the stability of growth factor receptors, such as PDGF-receptor-beta. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP5
?
Variant 7-31850714-C-A is Pathogenic according to our data. Variant chr7-31850714-C-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 433528.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
?
High AC in GnomAd at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDE1C | NM_001191057.4 | c.778G>T | p.Ala260Ser | missense_variant | 8/18 | ENST00000396191.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDE1C | ENST00000396191.6 | c.778G>T | p.Ala260Ser | missense_variant | 8/18 | 2 | NM_001191057.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152072Hom.: 0 Cov.: 31
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000478 AC: 12AN: 251008Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135652
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GnomAD4 exome AF: 0.0000110 AC: 16AN: 1460846Hom.: 0 Cov.: 29 AF XY: 0.0000110 AC XY: 8AN XY: 726736
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152072Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3AN XY: 74268
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ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hearing loss, autosomal dominant 74 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 12, 2018 | - - |
Autosomal dominant nonsyndromic hearing loss Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | Dr. Liu's Molecular Genetics Laboratory, University of Miami Miller School of Medicine | Aug 14, 2017 | The affected members show autosomal dominant progressive hearing loss. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
T;D;D;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;D;.;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D
Polyphen
1.0, 1.0
.;D;D;D;D
Vest4
MutPred
0.78
.;Gain of glycosylation at A260 (P = 0.0193);Gain of glycosylation at A260 (P = 0.0193);Gain of glycosylation at A260 (P = 0.0193);Gain of glycosylation at A260 (P = 0.0193);
MVP
MPC
ClinPred
T
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