chr15-85109113-C-G

Variant names:

• chr15-85109113-C-G
• NM_002605.3:c.1097C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002605.3(PDE8A):​c.1097C>G​(p.Ala366Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict 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: 0.0000014 (0 hom.)
• Consequence: PDE8A NM_002605.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30

Genes affected

PDE8A (HGNC:8793): (phosphodiesterase 8A) The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE8 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 found for this gene.[provided by RefSeq, Jul 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.086272925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE8A	NM_002605.3	c.1097C>G	p.Ala366Gly	missense_variant	Exon 12 of 22	ENST00000394553.6	NP_002596.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE8A	ENST00000394553.6	c.1097C>G	p.Ala366Gly	missense_variant	Exon 12 of 22	1	NM_002605.3	ENSP00000378056.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457734 Hom.: 0 Cov.: 27 AF XY: 0.00000276 AC XY: 2 AN XY: 725386

Gnomad4 AFR exome AF: 0.00

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	6.3
DANN	Benign	0.73
DEOGEN2	Benign	0.099	T;.;T;.
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.45	T;T;.;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.086	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.97	L;.;L;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.54	N;N;N;N
REVEL	Benign	0.10
Sift	Benign	0.33	T;T;T;T
Sift4G	Benign	0.20	T;T;T;T
Polyphen		0.0	B;.;B;B
Vest4		0.16
MutPred		0.18		Loss of helix (P = 0.0558);.;Loss of helix (P = 0.0558);.;
MVP		0.22
MPC		0.19
ClinPred		0.098	T
GERP RS		0.98
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.042
gMVP		0.21

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: chr15-85652344;