rs62362531

Variant names:

• chr5-77426617-C-T
• rs62362531
• NM_003719.5:c.*63C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003719.5(PDE8B):​c.*63C>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 0.14 in 852,860 control chromosomes in the GnomAD database, including 9,460 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1228 hom., cov: 32)
  • Exomes 𝑓: 0.15 (8232 hom.)
• Consequence: PDE8B NM_003719.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.559
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 5-77426617-C-T is Benign according to our data. Variant chr5-77426617-C-T is described in ClinVar as Benign. ClinVar VariationId is 354178.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.159 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.*63C>T		3_prime_UTR	Exon 22 of 22	NP_003710.1	O95263-1
	PDE8B	NM_001349749.3		c.*63C>T		3_prime_UTR	Exon 23 of 23	NP_001336678.1
	PDE8B	NM_001349748.3		c.*63C>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.*63C>T		3_prime_UTR	Exon 22 of 22	ENSP00000264917.6	O95263-1
	PDE8B	ENST00000342343.8	TSL:1	c.*63C>T		3_prime_UTR	Exon 21 of 21	ENSP00000345646.4	O95263-4
	PDE8B	ENST00000340978.7	TSL:1	c.*63C>T		3_prime_UTR	Exon 21 of 21	ENSP00000345446.3	O95263-6

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17291 AN: 152158 Hom.: 1226 Cov.: 32

Gnomad AFR AF: 0.0304

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.0973

Gnomad ASJ AF: 0.0562

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.110

GnomAD4 exome AF: 0.146 AC: 102098 AN: 700582 Hom.: 8232 Cov.: 9 AF XY: 0.147 AC XY: 55119 AN XY: 374176

African (AFR) AF: 0.0276 AC: 522 AN: 18890

American (AMR) AF: 0.0752 AC: 2955 AN: 39308

Ashkenazi Jewish (ASJ) AF: 0.0573 AC: 1211 AN: 21118

East Asian (EAS) AF: 0.118 AC: 4105 AN: 34920

South Asian (SAS) AF: 0.169 AC: 11539 AN: 68128

European-Finnish (FIN) AF: 0.161 AC: 8306 AN: 51658

Middle Eastern (MID) AF: 0.0807 AC: 344 AN: 4262

European-Non Finnish (NFE) AF: 0.160 AC: 68430 AN: 426912

Other (OTH) AF: 0.132 AC: 4686 AN: 35386

GnomAD4 genome AF: 0.114 AC: 17299 AN: 152278 Hom.: 1228 Cov.: 32 AF XY: 0.113 AC XY: 8434 AN XY: 74442

African (AFR) AF: 0.0303 AC: 1261 AN: 41564

American (AMR) AF: 0.0976 AC: 1493 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0562 AC: 195 AN: 3472

East Asian (EAS) AF: 0.137 AC: 711 AN: 5186

South Asian (SAS) AF: 0.168 AC: 813 AN: 4828

European-Finnish (FIN) AF: 0.161 AC: 1704 AN: 10596

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10765 AN: 68022

Other (OTH) AF: 0.113 AC: 239 AN: 2112

Alfa AF: 0.110 Hom.: 168

Bravo AF: 0.102

Asia WGS AF: 0.155 AC: 539 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Autosomal dominant striatal neurodegeneration type 1 (1)
-	-	1	not provided (1)
-	-	1	Striatal Degeneration (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.6
DANN	Benign	0.78
PhyloP100		-0.56
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: rs62362531; hg19: chr5-76722442; COSMIC: COSV53732071; COSMIC: COSV53732071;