19-18218153-G-A

Variant names:

• chr19-18218153-G-A
• rs151012513
• NM_001098818.4:c.1230C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001098818.4(PDE4C):​c.1230C>T​(p.Asn410Asn) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000822 in 1,460,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: PDE4C NM_001098818.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.05
• Publications: 3 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).

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.1230C>T	p.Asn410Asn	synonymous	Exon 11 of 15	NP_001092288.1	Q08493-3
	PDE4C	NM_000923.6		c.1326C>T	p.Asn442Asn	synonymous	Exon 12 of 16	NP_000914.2	Q08493-1
	PDE4C	NM_001330172.2		c.1326C>T	p.Asn442Asn	synonymous	Exon 12 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.1230C>T	p.Asn410Asn	synonymous	Exon 11 of 15	ENSP00000262805.10	Q08493-3
	PDE4C	ENST00000355502.7	TSL:2	c.1326C>T	p.Asn442Asn	synonymous	Exon 15 of 19	ENSP00000347689.2
	PDE4C	ENST00000594465.7	TSL:1	c.1326C>T	p.Asn442Asn	synonymous	Exon 11 of 15	ENSP00000470210.1	Q08493-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251130 AF XY: 0.0000147

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000822 AC: 12 AN: 1460278 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726412

African (AFR) AF: 0.0000897 AC: 3 AN: 33440

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1110590

Other (OTH) AF: 0.0000332 AC: 2 AN: 60320

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	9.9
DANN	Benign	0.71
PhyloP100		4.0

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

Other links and lift over

dbSNP: rs151012513; hg19: chr19-18328963;