NM_003719.5:c.52C>A

Variant names:

• chr5-77210977-C-A
• rs886060753
• NM_003719.5:c.52C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP7

The NM_003719.5(PDE8B):​c.52C>A​(p.Arg18Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDE8B NM_003719.5 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.412
• 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 Gene-Disease associations (from GenCC):

• autosomal dominant striatal neurodegeneration type 1

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• pigmented nodular adrenocortical disease, primary, 3

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• primary pigmented nodular adrenocortical disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• striatal degeneration, autosomal dominant

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

PDE8B (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP7: Synonymous conserved (PhyloP=0.412 with no splicing effect.

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.52C>A	p.Arg18Arg	synonymous	Exon 1 of 22	NP_003710.1	O95263-1
	PDE8B	NM_001349749.3		c.52C>A	p.Arg18Arg	synonymous	Exon 1 of 23	NP_001336678.1
	PDE8B	NM_001349748.3		c.52C>A	p.Arg18Arg	synonymous	Exon 1 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.52C>A	p.Arg18Arg	synonymous	Exon 1 of 22	ENSP00000264917.6	O95263-1
	PDE8B	ENST00000342343.8	TSL:1	c.52C>A	p.Arg18Arg	synonymous	Exon 1 of 21	ENSP00000345646.4	O95263-4
	PDE8B	ENST00000340978.7	TSL:1	c.52C>A	p.Arg18Arg	synonymous	Exon 1 of 21	ENSP00000345446.3	O95263-6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1387092 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 689284

African (AFR) AF: 0.00 AC: 0 AN: 28824

American (AMR) AF: 0.00 AC: 0 AN: 38048

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24100

East Asian (EAS) AF: 0.00 AC: 0 AN: 32708

South Asian (SAS) AF: 0.00 AC: 0 AN: 79964

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35930

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5372

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1084808

Other (OTH) AF: 0.00 AC: 0 AN: 57338

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Autosomal dominant striatal neurodegeneration type 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	15
DANN	Uncertain	0.98
PhyloP100		0.41
PromoterAI		-0.057	Neutral

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: rs886060753; hg19: chr5-76506802;