Variant chr7-31815963-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001191057.4(PDE1C):c.1774T>G(p.Ser592Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0052 in 1,613,802 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0044 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0053 ( 39 hom. )

Consequence

PDE1C
NM_001191057.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.00600

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004617542).

BP6

Variant 7-31815963-A-C is Benign according to our data. Variant chr7-31815963-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2657379.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 663 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE1C	NM_001191057.4 linkuse as main transcript	c.1774T>G	p.Ser592Ala	missense_variant	15/18	ENST00000396191.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE1C	ENST00000396191.6 linkuse as main transcript	c.1774T>G	p.Ser592Ala	missense_variant	15/18	2	NM_001191057.4	A1	Q14123-1

Frequencies

GnomAD3 genomes

AF:

0.00437

AC:

664

AN:

152008

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00472

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00528

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00687

Gnomad OTH

AF:

0.00336

GnomAD3 exomes

AF:

0.00415

AC:

1044

AN:

251368

Hom.:

AF XY:

0.00421

AC XY:

572

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.00367

Gnomad ASJ exome

AF:

0.00466

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00605

Gnomad NFE exome

AF:

0.00604

Gnomad OTH exome

AF:

0.00489

GnomAD4 exome

AF:

0.00529

AC:

7734

AN:

1461676

Hom.:

Cov.:

AF XY:

0.00516

AC XY:

3755

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.00123

Gnomad4 AMR exome

AF:

0.00389

Gnomad4 ASJ exome

AF:

0.00459

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00599

Gnomad4 NFE exome

AF:

0.00607

Gnomad4 OTH exome

AF:

0.00540

GnomAD4 genome

AF:

0.00436

AC:

663

AN:

152126

Hom.:

Cov.:

AF XY:

0.00421

AC XY:

313

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00116

Gnomad4 AMR

AF:

0.00471

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00528

Gnomad4 NFE

AF:

0.00685

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00575

Hom.:

Bravo

AF:

0.00416

ExAC

AF:

0.00385

AC:

468

EpiCase

AF:

0.00594

EpiControl

AF:

0.00688

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

PDE1C: BP4, BS2 -

PDE1C-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

CADD

Benign

2.5

DANN

Benign

0.65

DEOGEN2

Benign

0.24

T;T;T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.093

LIST_S2

Benign

0.54

T;.;T;.;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.0046

T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.34

.;N;N;N;N

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.27

N;N;N;N;N

REVEL

Benign

0.11

Sift

Benign

0.17

T;T;T;T;T

Sift4G

Benign

0.40

T;T;T;T;T

Polyphen

0.0

.;B;B;B;B

Vest4

0.10

MVP

0.35

MPC

0.026

ClinPred

0.0018

GERP RS

-3.4

Varity_R

0.050

gMVP

0.051

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over