Variant chr11-14644215-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000922.4(PDE3B):c.140T>G(p.Phe47Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000483 in 1,592,958 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

PDE3B
NM_000922.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.76

Variant links:

Genes affected

PDE3B (HGNC:8779): (phosphodiesterase 3B) Enables 3',5'-cyclic-nucleotide phosphodiesterase activity. Involved in negative regulation of angiogenesis; negative regulation of cell adhesion; and negative regulation of lipid catabolic process. Located in membrane. Part of guanyl-nucleotide exchange factor complex. [provided by Alliance of Genome Resources, Apr 2022]

PDE3B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE3B	NM_000922.4 link	c.140T>G	p.Phe47Cys	missense_variant	1/16	ENST00000282096.9	NP_000913.2	Q13370-1A7E2E5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PDE3B	ENST00000282096.9 link	c.140T>G	p.Phe47Cys	missense_variant	1/16	1	NM_000922.4	ENSP00000282096.4	Q13370-1
PDE3B	ENST00000455098.2 link	c.140T>G	p.Phe47Cys	missense_variant	1/16	1		ENSP00000388644.2	Q13370-2
PDE3B	ENST00000534317.1 link	n.-45T>G		upstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151610

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000946

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000464

AC:

AN:

215636

Hom.:

AF XY:

0.0000500

AC XY:

AN XY:

119896

show subpopulations

Gnomad AFR exome

AF:

0.0000842

Gnomad AMR exome

AF:

0.0000605

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000697

Gnomad FIN exome

AF:

0.000230

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000369

GnomAD4 exome

AF:

0.0000513

AC:

AN:

1441240

Hom.:

Cov.:

AF XY:

0.0000460

AC XY:

AN XY:

717080

show subpopulations

Gnomad4 AFR exome

AF:

0.0000307

Gnomad4 AMR exome

AF:

0.0000682

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000259

Gnomad4 SAS exome

AF:

0.0000471

Gnomad4 FIN exome

AF:

0.0000723

Gnomad4 NFE exome

AF:

0.0000532

Gnomad4 OTH exome

AF:

0.0000502

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151718

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74164

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000946

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000422

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 22, 2024

The c.140T>G (p.F47C) alteration is located in exon 1 (coding exon 1) of the PDE3B gene. This alteration results from a T to G substitution at nucleotide position 140, causing the phenylalanine (F) at amino acid position 47 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.37

T;.

Eigen

Benign

0.13

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.73

T;T

M_CAP

Pathogenic

0.93

MetaRNN

Uncertain

0.64

D;D

MetaSVM

Benign

-0.58

MutationAssessor

Benign

1.6

L;L

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.88

N;N

REVEL

Uncertain

0.30

Sift

Uncertain

0.0010

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.69

MVP

0.75

MPC

0.93

ClinPred

0.38

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.21

gMVP

0.51

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