Variant chr7-31809087-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001191057.4(PDE1C):c.1835A>G(p.Asn612Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,440,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PDE1C
NM_001191057.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.21

Variant links:

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]

PDE1C links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09969023).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE1C	NM_001191057.4 linkuse as main transcript	c.1835A>G	p.Asn612Ser	missense_variant	16/18	ENST00000396191.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE1C	ENST00000396191.6 linkuse as main transcript	c.1835A>G	p.Asn612Ser	missense_variant	16/18	2	NM_001191057.4	A1	Q14123-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1440186

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

717986

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000183

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PDE1C-related disorder

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 20, 2023

The PDE1C c.2015A>G variant is predicted to result in the amino acid substitution p.Asn672Ser. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

T;T;T;.;.

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.66

LIST_S2

Uncertain

0.91

D;.;D;.;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.10

T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.20

.;N;N;N;N

MutationTaster

Benign

0.99

N;N;N;N;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.25

N;N;N;N;N

REVEL

Benign

0.073

Sift

Benign

0.098

T;T;T;T;T

Sift4G

Uncertain

0.055

T;T;T;T;T

Polyphen

0.0020, 0.0070

.;B;B;B;B

Vest4

0.32

MutPred

0.10

.;Gain of phosphorylation at N612 (P = 0.0084);Gain of phosphorylation at N612 (P = 0.0084);Gain of phosphorylation at N612 (P = 0.0084);Gain of phosphorylation at N612 (P = 0.0084);

MVP

0.63

MPC

0.026

ClinPred

0.20

GERP RS

2.8

Varity_R

0.057

gMVP

0.13

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over