Genetic Variant PDE8B:c.*179G>A (chr5-77426733-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003719.5(PDE8B):c.*179G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000019 in 630,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

PDE8B
NM_003719.5 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0600

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 links:

PDE8B (HGNC:):

PDE8B links:

WDR41 (HGNC:25601): (WD repeat domain 41) Contributes to guanyl-nucleotide exchange factor activity. Involved in regulation of autophagy. Located in cytoplasm. Part of guanyl-nucleotide exchange factor complex. Colocalizes with Atg1/ULK1 kinase complex. [provided by Alliance of Genome Resources, Apr 2022]

WDR41 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BS2

High AC in GnomAdExome4 at 9 AD,Unknown gene.

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	Effect	Exon Rank	Protein	UniProt
PDE8B	NM_003719.5	MANE Select	c.*179G>A	3_prime_UTR	Exon 22 of 22	NP_003710.1	O95263-1
PDE8B	NM_001349749.3		c.*179G>A	3_prime_UTR	Exon 23 of 23	NP_001336678.1
PDE8B	NM_001349748.3		c.*179G>A	3_prime_UTR	Exon 22 of 22	NP_001336677.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PDE8B	ENST00000264917.10	TSL:1 MANE Select	c.*179G>A	3_prime_UTR	Exon 22 of 22	ENSP00000264917.6	O95263-1
PDE8B	ENST00000340978.7	TSL:1	c.*179G>A	3_prime_UTR	Exon 21 of 21	ENSP00000345446.3	O95263-6
PDE8B	ENST00000346042.7	TSL:1	c.*179G>A	3_prime_UTR	Exon 19 of 19	ENSP00000330428.3	O95263-2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000188

AC:

AN:

478570

Hom.:

Cov.:

AF XY:

0.0000195

AC XY:

AN XY:

256960

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

12690

American (AMR)

AF:

0.00

AC:

AN:

22268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15180

East Asian (EAS)

AF:

0.00

AC:

AN:

30334

South Asian (SAS)

AF:

0.00

AC:

AN:

49692

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38634

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2054

European-Non Finnish (NFE)

AF:

0.0000320

AC:

AN:

281214

Other (OTH)

AF:

0.00

AC:

AN:

26504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41444

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000340

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autosomal dominant striatal neurodegeneration type 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.2

(source)

DANN

Benign

0.57

PhyloP100

-0.060

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over