NM_003719.5:c.94G>A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 4P and 2B. PM2PM5BP4_Moderate

The NM_003719.5(PDE8B):c.94G>A(p.Val32Met) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V32A) has been classified as Pathogenic.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PDE8B
NM_003719.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.242

Publications

0 publications found

Variant links:

Genes affected

PDE8B (HGNC:8794): (phosphodiesterase 8B) The protein encoded by this gene is a cyclic nucleotide phosphodiesterase (PDE) that catalyzes the hydrolysis of the second messenger cAMP. The encoded protein, which does not hydrolyze cGMP, is resistant to several PDE inhibitors. Defects in this gene are a cause of autosomal dominant striatal degeneration (ADSD). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2010]

PDE8B Gene-Disease associations (from GenCC):

autosomal dominant striatal neurodegeneration type 1
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
pigmented nodular adrenocortical disease, primary, 3
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
primary pigmented nodular adrenocortical disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
striatal degeneration, autosomal dominant
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

PDE8B links:

PDE8B (HGNC:):

PDE8B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr5-77211020-T-C is described in ClinVar as Pathogenic. ClinVar VariationId is 1184955.Status of the report is criteria_provided_single_submitter, 1 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.18592018).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003719.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDE8B	NM_003719.5	MANE Select	c.94G>A	p.Val32Met	missense	Exon 1 of 22	NP_003710.1	O95263-1
PDE8B	NM_001349753.2		c.-276G>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 23	NP_001336682.1	A0A2R8Y4E6
PDE8B	NM_001349749.3		c.94G>A	p.Val32Met	missense	Exon 1 of 23	NP_001336678.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDE8B	ENST00000264917.10	TSL:1 MANE Select	c.94G>A	p.Val32Met	missense	Exon 1 of 22	ENSP00000264917.6	O95263-1
PDE8B	ENST00000342343.8	TSL:1	c.94G>A	p.Val32Met	missense	Exon 1 of 21	ENSP00000345646.4	O95263-4
PDE8B	ENST00000340978.7	TSL:1	c.94G>A	p.Val32Met	missense	Exon 1 of 21	ENSP00000345446.3	O95263-6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1396120

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

693280

African (AFR)

AF:

0.00

AC:

AN:

29212

American (AMR)

AF:

0.00

AC:

AN:

39282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24488

East Asian (EAS)

AF:

0.00

AC:

AN:

34158

South Asian (SAS)

AF:

0.00

AC:

AN:

80352

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35704

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5490

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1089422

Other (OTH)

AF:

0.00

AC:

AN:

58012

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.035

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.17

LIST_S2

Uncertain

0.87

M_CAP

Pathogenic

0.48

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.81

MutationAssessor

Benign

0.0

PhyloP100

0.24

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

0.040

REVEL

Benign

0.14

Sift

Benign

0.090

Sift4G

Benign

0.20

Polyphen

0.50

Vest4

0.17

MutPred

0.46

Loss of glycosylation at S31 (P = 0.1033)

MVP

0.39

MPC

1.1

ClinPred

0.29

GERP RS

1.8

PromoterAI

0.068

Neutral

(source)

Varity_R

0.069

gMVP

0.20

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over