Variant chr5-77211020-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PM2PP2PP5_ModerateBP4

The NM_003719.5(PDE8B):c.95T>C(p.Val32Ala) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Consequence

PDE8B
NM_003719.5 missense

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 2.63

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 links:

ENSG00000284762 (HGNC:):

ENSG00000284762 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), PDE8B. . Gene score misZ 2.9973 (greater than the threshold 3.09). Trascript score misZ 3.3776 (greater than threshold 3.09). GenCC has associacion of gene with pigmented nodular adrenocortical disease, primary, 3, autosomal dominant striatal neurodegeneration type 1, primary pigmented nodular adrenocortical disease, schizophrenia, striatal degeneration, autosomal dominant.

PP5

Variant 5-77211020-T-C is Pathogenic according to our data. Variant chr5-77211020-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 1184955.Status of the report is criteria_provided_single_submitter, 1 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.121973544). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE8B	NM_003719.5 link	c.95T>C	p.Val32Ala	missense_variant	1/22	ENST00000264917.10	NP_003710.1	O95263-1B3KN77

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE8B	ENST00000264917.10 link	c.95T>C	p.Val32Ala	missense_variant	1/22	1	NM_003719.5	ENSP00000264917.6		O95263-1
ENSG00000284762	ENST00000646262.1 link	c.-34+92499T>C		intron_variant				ENSP00000493971.1		A0A2R8Y4E6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen

Jun 17, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.038

.;.;T;.;.

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.83

T;T;T;T;T

M_CAP

Pathogenic

0.45

MetaRNN

Benign

0.12

T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

N;N;N;N;N

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

0.0

N;N;N;N;N

REVEL

Benign

0.17

Sift

Benign

0.24

T;T;T;T;T

Sift4G

Benign

0.54

T;T;T;T;T

Polyphen

0.0

B;B;B;B;B

Vest4

0.086

MutPred

0.47

Gain of relative solvent accessibility (P = 0.0249);Gain of relative solvent accessibility (P = 0.0249);Gain of relative solvent accessibility (P = 0.0249);Gain of relative solvent accessibility (P = 0.0249);Gain of relative solvent accessibility (P = 0.0249);

MVP

0.16

MPC

0.94

ClinPred

0.13

GERP RS

0.19

Varity_R

0.082

gMVP

0.27

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over