11-14644467-T-G

Position:

• chr11-14644467-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000922.4(PDE3B):​c.392T>G​(p.Phe131Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 5.18

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.887

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE3B	NM_000922.4	c.392T>G	p.Phe131Cys	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.392T>G	p.Phe131Cys	missense_variant	1/16	1	NM_000922.4	ENSP00000282096.4
PDE3B	ENST00000455098.2	c.392T>G	p.Phe131Cys	missense_variant	1/16	1		ENSP00000388644.2
PDE3B	ENST00000534317.1	n.208T>G		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

Ambry Genetics

Dec 07, 2021

The c.392T>G (p.F131C) 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 392, causing the phenylalanine (F) at amino acid position 131 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	Pathogenic	0.76
BayesDel_addAF	Uncertain	0.095	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.52	D;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Pathogenic	0.83	D
MetaRNN	Pathogenic	0.89	D;D
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	1.9	L;L
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-2.2	N;N
REVEL	Uncertain	0.56
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;.
Vest4		0.82
MutPred		0.63		Gain of catalytic residue at L132 (P = 0.0156);Gain of catalytic residue at L132 (P = 0.0156);
MVP		0.86
MPC		0.95
ClinPred		0.94	D
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.44
gMVP		0.63

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-14666013;