Genetic Variant NM_003719.5:c.4G>A (chr5-77210929-G-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_003719.5(PDE8B):c.4G>A(p.Gly2Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

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: 5.70

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.787

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.4G>A	p.Gly2Ser	missense	Exon 1 of 22	NP_003710.1	O95263-1
PDE8B	NM_001349749.3		c.4G>A	p.Gly2Ser	missense	Exon 1 of 23	NP_001336678.1
PDE8B	NM_001349748.3		c.4G>A	p.Gly2Ser	missense	Exon 1 of 22	NP_001336677.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDE8B	ENST00000264917.10	TSL:1 MANE Select	c.4G>A	p.Gly2Ser	missense	Exon 1 of 22	ENSP00000264917.6	O95263-1
PDE8B	ENST00000342343.8	TSL:1	c.4G>A	p.Gly2Ser	missense	Exon 1 of 21	ENSP00000345646.4	O95263-4
PDE8B	ENST00000340978.7	TSL:1	c.4G>A	p.Gly2Ser	missense	Exon 1 of 21	ENSP00000345446.3	O95263-6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1321868

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

654358

African (AFR)

AF:

0.00

AC:

AN:

27774

American (AMR)

AF:

0.00

AC:

AN:

29914

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22426

East Asian (EAS)

AF:

0.00

AC:

AN:

29528

South Asian (SAS)

AF:

0.00

AC:

AN:

71222

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33030

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4438

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1049482

Other (OTH)

AF:

0.00

AC:

AN:

54054

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

Pathogenic

0.88

BayesDel_addAF

Uncertain

0.096

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.27

Eigen_PC

Benign

0.21

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.94

M_CAP

Pathogenic

0.92

MetaRNN

Pathogenic

0.79

MetaSVM

Uncertain

0.43

MutationAssessor

Benign

0.81

PhyloP100

5.7

PrimateAI

Pathogenic

0.91

PROVEAN

Uncertain

-2.4

REVEL

Uncertain

0.64

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.67

MutPred

0.79

Gain of phosphorylation at G2 (P = 0.0526)

MVP

0.86

MPC

1.9

ClinPred

0.97

GERP RS

2.7

PromoterAI

-0.026

Neutral

(source)

Varity_R

0.68

gMVP

0.45

Mutation Taster

=61/39

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