NM_003719.5:c.339+10893G>C

Variant names:

• chr5-77222157-G-C
• rs13158164
• NM_003719.5:c.339+10893G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003719.5(PDE8B):​c.339+10893G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,250 control chromosomes in the GnomAD database, including 1,100 homozygotes. 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: 𝑓 0.10 (1100 hom., cov: 32)
• Consequence: PDE8B NM_003719.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.981
• Publications: 6 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

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.339+10893G>C		intron	N/A	NP_003710.1	O95263-1
	PDE8B	NM_001349749.3		c.339+10893G>C		intron	N/A	NP_001336678.1
	PDE8B	NM_001349748.3		c.339+10893G>C		intron	N/A	NP_001336677.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE8B	ENST00000264917.10	TSL:1 MANE Select	c.339+10893G>C		intron	N/A	ENSP00000264917.6	O95263-1
	PDE8B	ENST00000342343.8	TSL:1	c.339+10893G>C		intron	N/A	ENSP00000345646.4	O95263-4
	PDE8B	ENST00000340978.7	TSL:1	c.339+10893G>C		intron	N/A	ENSP00000345446.3	O95263-6

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15499 AN: 152132 Hom.: 1101 Cov.: 32

Gnomad AFR AF: 0.0268

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0841

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.107

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.102 AC: 15502 AN: 152250 Hom.: 1100 Cov.: 32 AF XY: 0.101 AC XY: 7531 AN XY: 74450

African (AFR) AF: 0.0267 AC: 1111 AN: 41562

American (AMR) AF: 0.186 AC: 2840 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 531 AN: 3472

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5184

South Asian (SAS) AF: 0.0840 AC: 405 AN: 4822

European-Finnish (FIN) AF: 0.125 AC: 1329 AN: 10604

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8952 AN: 67996

Other (OTH) AF: 0.106 AC: 225 AN: 2116

Alfa AF: 0.0704 Hom.: 106

Bravo AF: 0.100

Asia WGS AF: 0.0420 AC: 148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.3
DANN	Benign	0.53
PhyloP100		0.98
Mutation Taster		=100/0	polymorphism (auto)

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: rs13158164; hg19: chr5-76517982;