Variant chr11-14644110-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4

The NM_000922.4(PDE3B):c.35G>T(p.Arg12Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000183 in 1,421,168 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000018 ( 1 hom. )

Consequence

PDE3B
NM_000922.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.46

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM1

In a mutagenesis_site Loss of interaction with RAPGEF3. (size 0) in uniprot entity PDE3B_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27853048).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE3B	NM_000922.4 link	c.35G>T	p.Arg12Leu	missense_variant	1/16	ENST00000282096.9	NP_000913.2	Q13370-1A7E2E5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE3B	ENST00000282096.9 link	c.35G>T	p.Arg12Leu	missense_variant	1/16	1	NM_000922.4	ENSP00000282096.4		Q13370-1
PDE3B	ENST00000455098.2 link	c.35G>T	p.Arg12Leu	missense_variant	1/16	1		ENSP00000388644.2		Q13370-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000574

AC:

AN:

191636

Hom.:

AF XY:

0.0000840

AC XY:

AN XY:

107086

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000339

Gnomad FIN exome

AF:

0.000104

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000206

GnomAD4 exome

AF:

0.0000183

AC:

AN:

1421168

Hom.:

Cov.:

AF XY:

0.0000311

AC XY:

AN XY:

706328

show subpopulations

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:

0.000289

Gnomad4 FIN exome

AF:

0.0000266

Gnomad4 NFE exome

AF:

9.08e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000508

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

Jun 07, 2023

The c.35G>T (p.R12L) alteration is located in exon 1 (coding exon 1) of the PDE3B gene. This alteration results from a G to T substitution at nucleotide position 35, causing the arginine (R) at amino acid position 12 to be replaced by a leucine (L). 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

Benign

0.18

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.31

T;.

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.63

T;T

M_CAP

Pathogenic

0.96

MetaRNN

Benign

0.28

T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.1

L;L

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.72

N;N

REVEL

Benign

0.12

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.018

D;D

Polyphen

0.84

P;.

Vest4

0.43

MutPred

0.21

Loss of MoRF binding (P = 0.0217);Loss of MoRF binding (P = 0.0217);

MVP

0.67

MPC

0.87

ClinPred

0.20

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.32

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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