chr11-14644551-C-T

Position:

• chr11-14644551-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000922.4(PDE3B):​c.476C>T​(p.Ala159Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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)
• Consequence: PDE3B NM_000922.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.44

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34009477).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE3B	NM_000922.4	c.476C>T	p.Ala159Val	missense_variant	1/16	ENST00000282096.9	NP_000913.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE3B	ENST00000282096.9	c.476C>T	p.Ala159Val	missense_variant	1/16	1	NM_000922.4	ENSP00000282096.4
PDE3B	ENST00000455098.2	c.476C>T	p.Ala159Val	missense_variant	1/16	1		ENSP00000388644.2
PDE3B	ENST00000534317.1	n.292C>T		non_coding_transcript_exon_variant	1/2	1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

May 22, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.78	T;T
M_CAP	Pathogenic	0.49	D
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.58	N;N
REVEL	Benign	0.14
Sift	Benign	0.11	T;T
Sift4G	Benign	0.44	T;T
Polyphen		0.58	P;.
Vest4		0.22
MutPred		0.32		Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);
MVP		0.64
MPC		0.20
ClinPred		0.70	D
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.35

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

Other links and lift over

dbSNP: rs1590023524; hg19: chr11-14666097;