PDE4C p.Glu291Glu

Variant names:

• chr19-18219035-G-G
• NM_001098818.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr19-18219036--
• chr19-18219036-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001098818.4(PDE4C):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDE4C NM_001098818.4 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.672
• Publications: 0 publications found

Genes affected

PDE4C (HGNC:8782): (phosphodiesterase 4C) The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE4 subfamily. This PDE hydrolyzes the second messenger, cAMP, which is a regulator and mediator of a number of cellular responses to extracellular signals. Thus, by regulating the cellular concentration of cAMP, this protein plays a key role in many important physiological processes. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.[provided by RefSeq, Jul 2011]

PDE4C (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098818.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4C	NM_001098818.4	MANE Select	c.		exon_region	Exon 9 of 15	NP_001092288.1	Q08493-3
	PDE4C	NM_000923.6		c.		exon_region	Exon 10 of 16	NP_000914.2	Q08493-1
	PDE4C	NM_001330172.2		c.		exon_region	Exon 10 of 16	NP_001317101.1	Q08493-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4C	ENST00000262805.17	TSL:1 MANE Select	c.		exon_region	Exon 9 of 15	ENSP00000262805.10	Q08493-3
	PDE4C	ENST00000355502.7	TSL:2	c.		exon_region	Exon 13 of 19	ENSP00000347689.2
	PDE4C	ENST00000594465.7	TSL:1	c.		exon_region	Exon 9 of 15	ENSP00000470210.1	Q08493-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-18329845;