11-14644186-C-A

Position:

• chr11-14644186-C-A

Variant summary

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

The NM_000922.4(PDE3B):​c.111C>A​(p.Ser37Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,226 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PDE3B NM_000922.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.64

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 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	c.111C>A	p.Ser37Arg	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.111C>A	p.Ser37Arg	missense_variant	1/16	1	NM_000922.4	ENSP00000282096.4
PDE3B	ENST00000455098.2	c.111C>A	p.Ser37Arg	missense_variant	1/16	1		ENSP00000388644.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1445226 Hom.: 0 Cov.: 33 AF XY: 0.00000139 AC XY: 1 AN XY: 719418

Gnomad4 AFR exome AF: 0.0000306

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Nov 09, 2024

The c.111C>A (p.S37R) alteration is located in exon 1 (coding exon 1) of the PDE3B gene. This alteration results from a C to A substitution at nucleotide position 111, causing the serine (S) at amino acid position 37 to be replaced by an arginine (R). 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	0.69
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T;.
Eigen	Benign	0.028
Eigen_PC	Benign	0.038
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Pathogenic	0.95	D
MetaRNN	Uncertain	0.50	T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.89	N;N
REVEL	Benign	0.10
Sift	Benign	0.090	T;T
Sift4G	Benign	0.14	T;T
Polyphen		0.94	P;.
Vest4		0.49
MutPred		0.22		Gain of MoRF binding (P = 0.0186);Gain of MoRF binding (P = 0.0186);
MVP		0.61
MPC		0.38
ClinPred		0.80	D
GERP RS		2.4
Varity_R		0.17
gMVP		0.47

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: chr11-14665732;