rs865924081

Variant names:

• chr15-85100169-C-A
• rs865924081
• NM_002605.3:c.1007C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-85100169-C-A
• chr15-85100169-C-G
• chr15-85100169-C-T

Variant summary

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

The NM_002605.3(PDE8A):​c.1007C>A​(p.Ser336Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S336P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PDE8A NM_002605.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.788
• Publications: 0 publications found

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

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 (MetaRNN=0.09938413).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002605.3. 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
	PDE8A	NM_002605.3	MANE Select	c.1007C>A	p.Ser336Tyr	missense	Exon 11 of 22	NP_002596.1	O60658-1
	PDE8A	NM_173454.1		c.869C>A	p.Ser290Tyr	missense	Exon 10 of 21	NP_775656.1	O60658-2
	PDE8A	NM_001243137.2		c.791C>A	p.Ser264Tyr	missense	Exon 11 of 22	NP_001230066.1	O60658-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE8A	ENST00000394553.6	TSL:1 MANE Select	c.1007C>A	p.Ser336Tyr	missense	Exon 11 of 22	ENSP00000378056.1	O60658-1
	PDE8A	ENST00000310298.8	TSL:1	c.1007C>A	p.Ser336Tyr	missense	Exon 12 of 23	ENSP00000311453.4	O60658-1
	PDE8A	ENST00000339708.9	TSL:1	c.869C>A	p.Ser290Tyr	missense	Exon 10 of 21	ENSP00000340679.5	O60658-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	8.9
DANN	Benign	0.21
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.79
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.13
Sift	Benign	0.58	T
Sift4G	Benign	0.081	T
Polyphen		0.16	B
Vest4		0.21
MutPred		0.45		Loss of disorder (P = 0.0062)
MVP		0.20
MPC		0.30
ClinPred		0.049	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.037
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs865924081; hg19: chr15-85643400;