Genetic Variant PDE8B:c.*439C>T (chr5-77426993-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003719.5(PDE8B):c.*439C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000745 in 186,474 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 Benign (★).

Frequency

Genomes: 𝑓 0.00080 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00052 ( 0 hom. )

Consequence

PDE8B
NM_003719.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.129

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 5-77426993-C-T is Benign according to our data. Variant chr5-77426993-C-T is described in ClinVar as Benign. ClinVar VariationId is 354186.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 120 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.*439C>T	3_prime_UTR	Exon 22 of 22	NP_003710.1	O95263-1
PDE8B	NM_001349749.3		c.*439C>T	3_prime_UTR	Exon 23 of 23	NP_001336678.1
PDE8B	NM_001349748.3		c.*439C>T	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.*439C>T	3_prime_UTR	Exon 22 of 22	ENSP00000264917.6	O95263-1
PDE8B	ENST00000340978.7	TSL:1	c.*439C>T	3_prime_UTR	Exon 21 of 21	ENSP00000345446.3	O95263-6
PDE8B	ENST00000346042.7	TSL:1	c.*439C>T	3_prime_UTR	Exon 19 of 19	ENSP00000330428.3	O95263-2

Frequencies

GnomAD3 genomes

AF:

0.000800

AC:

120

AN:

150076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000295

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000596

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000217

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00143

Gnomad OTH

AF:

0.000484

GnomAD4 exome

AF:

0.000524

AC:

AN:

36278

Hom.:

Cov.:

AF XY:

0.000543

AC XY:

AN XY:

18424

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

872

American (AMR)

AF:

0.00157

AC:

AN:

3176

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

750

East Asian (EAS)

AF:

0.00

AC:

AN:

2270

South Asian (SAS)

AF:

0.00

AC:

AN:

4066

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000548

AC:

AN:

21882

Other (OTH)

AF:

0.00112

AC:

AN:

1786

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

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:

0.000799

AC:

120

AN:

150196

Hom.:

Cov.:

AF XY:

0.000655

AC XY:

AN XY:

73236

show subpopulations

African (AFR)

AF:

0.000294

AC:

AN:

40752

American (AMR)

AF:

0.000595

AC:

AN:

15116

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

4908

South Asian (SAS)

AF:

0.000217

AC:

AN:

4616

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10244

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00143

AC:

AN:

67808

Other (OTH)

AF:

0.000479

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.000164

Hom.:

Bravo

AF:

0.000831

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

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

-0.84

CADD

Benign

1.2

(source)

DANN

Benign

0.69

PhyloP100

-0.13

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