15-85064410-A-C

Variant names:

• chr15-85064410-A-C
• NM_002605.3:c.227A>C

Variant summary

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

The NM_002605.3(PDE8A):​c.227A>C​(p.His76Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,220 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: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PDE8A NM_002605.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77

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=0.20599926).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE8A	NM_002605.3	c.227A>C	p.His76Pro	missense_variant	Exon 2 of 22	ENST00000394553.6	NP_002596.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE8A	ENST00000394553.6	c.227A>C	p.His76Pro	missense_variant	Exon 2 of 22	1	NM_002605.3	ENSP00000378056.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455220 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 724428

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: 9.04e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.061	T;.;T;.
Eigen	Benign	-0.0013
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.83	T;T;.;T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.6	L;.;L;L
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.8	N;N;N;N
REVEL	Uncertain	0.35
Sift	Benign	0.26	T;T;T;T
Sift4G	Benign	0.22	T;T;T;T
Polyphen		0.98	D;.;D;B
Vest4		0.50
MutPred		0.39		Loss of sheet (P = 0.0457);.;Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);
MVP		0.40
MPC		0.81
ClinPred		0.86	D
GERP RS		4.5
Varity_R		0.16
gMVP		0.43

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: chr15-85607641;