7-31809058-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001191057.4(PDE1C):c.1864A>G(p.Ile622Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000408 in 1,591,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. I622I) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

PDE1C
NM_001191057.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.234

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hearing loss, autosomal dominant 74
Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

PDE1C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016542941).

BP6

Variant 7-31809058-T-C is Benign according to our data. Variant chr7-31809058-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3416190.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 26 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001191057.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDE1C	NM_001191057.4	MANE Select	c.1864A>G	p.Ile622Val	missense	Exon 16 of 18	NP_001177986.1	Q14123-1
PDE1C	NM_001191058.4		c.2044A>G	p.Ile682Val	missense	Exon 17 of 19	NP_001177987.2	A0A0A0MS69
PDE1C	NM_001322059.2		c.2269A>G	p.Ile757Val	missense	Exon 17 of 18	NP_001308988.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDE1C	ENST00000396191.6	TSL:2 MANE Select	c.1864A>G	p.Ile622Val	missense	Exon 16 of 18	ENSP00000379494.1	Q14123-1
PDE1C	ENST00000396182.6	TSL:1	c.1864A>G	p.Ile622Val	missense	Exon 16 of 17	ENSP00000379485.2	Q14123-2
PDE1C	ENST00000396184.7	TSL:1	c.1864A>G	p.Ile622Val	missense	Exon 17 of 18	ENSP00000379487.3	Q14123-2

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

151980

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000441

AC:

AN:

249582

AF XY:

0.0000370

show subpopulations

Gnomad AFR exome

AF:

0.000680

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000271

AC:

AN:

1439794

Hom.:

Cov.:

AF XY:

0.0000209

AC XY:

AN XY:

717694

show subpopulations

African (AFR)

AF:

0.000758

AC:

AN:

32998

American (AMR)

AF:

0.00

AC:

AN:

44548

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25888

East Asian (EAS)

AF:

0.00

AC:

AN:

39376

South Asian (SAS)

AF:

0.00

AC:

AN:

85672

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53114

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5648

European-Non Finnish (NFE)

AF:

0.0000110

AC:

AN:

1092968

Other (OTH)

AF:

0.0000336

AC:

AN:

59582

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.420

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000171

AC:

AN:

151980

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74224

show subpopulations

African (AFR)

AF:

0.000579

AC:

AN:

41428

American (AMR)

AF:

0.0000657

AC:

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67934

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000133

Hom.:

Bravo

AF:

0.000185

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000547

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.66

(source)

DANN

Benign

0.35

DEOGEN2

Benign

0.20

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.0048

LIST_S2

Benign

0.69

M_CAP

Benign

0.013

MetaRNN

Benign

0.017

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.23

PrimateAI

Benign

0.24

PROVEAN

Benign

0.040

REVEL

Benign

0.12

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.037

MVP

0.35

MPC

0.026

ClinPred

0.0030

GERP RS

2.2

Varity_R

0.034

gMVP

0.053

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over