chr5-77426990-C-T

Variant names:

• chr5-77426990-C-T
• rs144907726
• NM_003719.5:c.*436C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_003719.5(PDE8B):​c.*436C>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 0.000106 in 188,822 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000094 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: PDE8B NM_003719.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.231
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS2: High AC in GnomAd4 at 14 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE8B	NM_003719.5	MANE Select	c.*436C>T		3_prime_UTR	Exon 22 of 22	NP_003710.1	O95263-1
	PDE8B	NM_001349749.3		c.*436C>T		3_prime_UTR	Exon 23 of 23	NP_001336678.1
	PDE8B	NM_001349748.3		c.*436C>T		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.*436C>T		3_prime_UTR	Exon 22 of 22	ENSP00000264917.6	O95263-1
	PDE8B	ENST00000340978.7	TSL:1	c.*436C>T		3_prime_UTR	Exon 21 of 21	ENSP00000345446.3	O95263-6
	PDE8B	ENST00000346042.7	TSL:1	c.*436C>T		3_prime_UTR	Exon 19 of 19	ENSP00000330428.3	O95263-2

Frequencies

GnomAD3 genomes AF: 0.0000945 AC: 14 AN: 148226 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000149

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000671

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00152

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000148 AC: 6 AN: 40460 Hom.: 0 Cov.: 0 AF XY: 0.000144 AC XY: 3 AN XY: 20766

African (AFR) AF: 0.00 AC: 0 AN: 958

American (AMR) AF: 0.00 AC: 0 AN: 3276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 888

East Asian (EAS) AF: 0.00238 AC: 6 AN: 2516

South Asian (SAS) AF: 0.00 AC: 0 AN: 4712

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 118

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 24374

Other (OTH) AF: 0.00 AC: 0 AN: 1988

GnomAD4 genome AF: 0.0000944 AC: 14 AN: 148362 Hom.: 0 Cov.: 32 AF XY: 0.0000553 AC XY: 4 AN XY: 72336

African (AFR) AF: 0.000149 AC: 6 AN: 40276

American (AMR) AF: 0.0000670 AC: 1 AN: 14930

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00152 AC: 7 AN: 4608

South Asian (SAS) AF: 0.00 AC: 0 AN: 4382

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67362

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

Asia WGS AF: 0.000577 AC: 2 AN: 3478

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	Benign	-0.83
CADD	Benign	7.4
DANN	Benign	0.75
PhyloP100		0.23

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: rs144907726; hg19: chr5-76722815;