rs566925510

Variant names:

• chr5-77426611-C-A
• rs566925510
• NM_003719.5:c.*57C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-77426611-C-A
• chr5-77426611-C-T

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.*57C>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 0.00000137 in 732,278 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PDE8B NM_003719.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.729
• 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=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE8B	NM_003719.5	c.*57C>A		3_prime_UTR_variant	Exon 22 of 22	ENST00000264917.10	NP_003710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE8B	ENST00000264917.10	c.*57C>A		3_prime_UTR_variant	Exon 22 of 22	1	NM_003719.5	ENSP00000264917.6
PDE8B	ENST00000646262.1	c.*57C>A		3_prime_UTR_variant	Exon 24 of 24			ENSP00000493971.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 1 AN: 732278 Hom.: 0 Cov.: 10 AF XY: 0.00000257 AC XY: 1 AN XY: 389812

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 19358

American (AMR) AF: 0.00 AC: 0 AN: 40174

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21382

East Asian (EAS) AF: 0.00 AC: 0 AN: 35394

South Asian (SAS) AF: 0.00 AC: 0 AN: 69260

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52058

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4326

European-Non Finnish (NFE) AF: 0.00000220 AC: 1 AN: 453904

Other (OTH) AF: 0.00 AC: 0 AN: 36422

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.38
DANN	Benign	0.73
PhyloP100		-0.73

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: rs566925510; hg19: chr5-76722436;