5-77426993-C-A

Variant names:

• chr5-77426993-C-A
• rs564968394
• NM_003719.5:c.*439C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003719.5(PDE8B):​c.*439C>A variant causes a 3 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDE8B NM_003719.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129
• Publications: 0 publications found

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 (HGNC:):

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE8B	NM_003719.5	MANE Select	c.*439C>A		3_prime_UTR	Exon 22 of 22	NP_003710.1	O95263-1
	PDE8B	NM_001349749.3		c.*439C>A		3_prime_UTR	Exon 23 of 23	NP_001336678.1
	PDE8B	NM_001349748.3		c.*439C>A		3_prime_UTR	Exon 22 of 22	NP_001336677.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE8B	ENST00000264917.10	TSL:1 MANE Select	c.*439C>A		3_prime_UTR	Exon 22 of 22	ENSP00000264917.6	O95263-1
	PDE8B	ENST00000340978.7	TSL:1	c.*439C>A		3_prime_UTR	Exon 21 of 21	ENSP00000345446.3	O95263-6
	PDE8B	ENST00000346042.7	TSL:1	c.*439C>A		3_prime_UTR	Exon 19 of 19	ENSP00000330428.3	O95263-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 36278 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 18424

African (AFR) AF: 0.00 AC: 0 AN: 872

American (AMR) AF: 0.00 AC: 0 AN: 3176

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 750

East Asian (EAS) AF: 0.00 AC: 0 AN: 2270

South Asian (SAS) AF: 0.00 AC: 0 AN: 4066

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 98

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 21882

Other (OTH) AF: 0.00 AC: 0 AN: 1786

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.60
DANN	Benign	0.63
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

Other links and lift over

dbSNP: rs564968394; hg19: chr5-76722818;