rs148606596

Variant names:

• chr7-31753535-C-A
• NM_001191057.4:c.1979G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-31753535-C-A
• chr7-31753535-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001191057.4(PDE1C):​c.1979G>T​(p.Arg660Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,457,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PDE1C NM_001191057.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49

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 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=0.18600354).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE1C	NM_001191057.4	c.1979G>T	p.Arg660Leu	missense_variant	Exon 18 of 18	ENST00000396191.6	NP_001177986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE1C	ENST00000396191.6	c.1979G>T	p.Arg660Leu	missense_variant	Exon 18 of 18	2	NM_001191057.4	ENSP00000379494.1
PDE1C	ENST00000396193.5	c.2159G>T	p.Arg720Leu	missense_variant	Exon 19 of 19	2		ENSP00000379496.1
PDE1C	ENST00000321453.12	c.1979G>T	p.Arg660Leu	missense_variant	Exon 19 of 19	2		ENSP00000318105.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1457772 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725058

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T;T;T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.84	T;.;T
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.69	.;N;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.25	N;N;N
REVEL	Uncertain	0.37
Sift	Uncertain	0.028	D;D;D
Sift4G	Uncertain	0.028	D;D;D
Polyphen		0.057	.;B;B
Vest4		0.36
MutPred		0.35		.;Loss of MoRF binding (P = 6e-04);Loss of MoRF binding (P = 6e-04);
MVP		0.73
MPC		0.041
ClinPred		0.76	D
GERP RS		4.5
Varity_R		0.073
gMVP		0.37

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-31793149;