7-31775712-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001191057.4(PDE1C):c.1912G>A(p.Gly638Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,612,688 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (50 hom.)
• Consequence: PDE1C NM_001191057.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.390

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002098769).
• BP6: Variant 7-31775712-C-T is Benign according to our data. Variant chr7-31775712-C-T is described in ClinVar as [Benign]. Clinvar id is 3038497.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE1C	NM_001191057.4	c.1912G>A	p.Gly638Ser	missense_variant	17/18	ENST00000396191.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE1C	ENST00000396191.6	c.1912G>A	p.Gly638Ser	missense_variant	17/18	2	NM_001191057.4	A1
PDE1C	ENST00000396193.5	c.2092G>A	p.Gly698Ser	missense_variant	18/19	2		A1
PDE1C	ENST00000321453.12	c.1912G>A	p.Gly638Ser	missense_variant	18/19	2		A1

Frequencies

GnomAD3 genomes AF: 0.00237 AC: 360 AN: 152030 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.000677

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0585

Gnomad SAS AF: 0.00229

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00519 AC: 1253 AN: 241536 Hom.: 45 AF XY: 0.00475 AC XY: 630 AN XY: 132608

Gnomad AFR exome AF: 0.000490

Gnomad AMR exome AF: 0.000233

Gnomad ASJ exome AF: 0.000302

Gnomad EAS exome AF: 0.0659

Gnomad SAS exome AF: 0.00112

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.000103

Gnomad OTH exome AF: 0.00201

GnomAD4 exome AF: 0.00168 AC: 2447 AN: 1460540 Hom.: 50 Cov.: 30 AF XY: 0.00163 AC XY: 1185 AN XY: 726564

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.000268

Gnomad4 ASJ exome AF: 0.000306

Gnomad4 EAS exome AF: 0.0512

Gnomad4 SAS exome AF: 0.00131

Gnomad4 FIN exome AF: 0.0000956

Gnomad4 NFE exome AF: 0.000103

Gnomad4 OTH exome AF: 0.00250

GnomAD4 genome AF: 0.00235 AC: 357 AN: 152148 Hom.: 8 Cov.: 32 AF XY: 0.00265 AC XY: 197 AN XY: 74378

Gnomad4 AFR AF: 0.000675

Gnomad4 AMR AF: 0.000458

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.0580

Gnomad4 SAS AF: 0.00229

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000439 Hom.: 1

Bravo AF: 0.00292

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.00515 AC: 604

Asia WGS AF: 0.0170 AC: 58 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

PDE1C-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 04, 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	0.077
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.43
Cadd	Benign	5.3
Dann	Benign	0.57
DEOGEN2	Benign	0.22	T;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.78	T;.;T
MetaRNN	Benign	0.0021	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.13	N;N;N
REVEL	Benign	0.15
Sift	Benign	0.26	T;T;T
Sift4G	Benign	0.52	T;T;T
Polyphen		0.25	.;B;B
Vest4		0.28
MVP		0.38
MPC		0.029
ClinPred		0.0062	T
GERP RS		2.6
Varity_R		0.033
gMVP		0.24

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs74905175; hg19: chr7-31815326; COSMIC: COSV58515013;