rs484594

Variant names:

• chr6-165535063-G-A
• rs484594
• NM_001385079.1:c.994+8377C>T

Variant summary

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

The NM_001385079.1(PDE10A):​c.994+8377C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 151,842 control chromosomes in the GnomAD database, including 39,665 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 0.69 (39665 hom., cov: 31)
• Consequence: PDE10A NM_001385079.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.670
• Publications: 2 publications found

Genes affected

PDE10A (HGNC:8772): (phosphodiesterase 10A) The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase family. It plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This protein can hydrolyze both cAMP and cGMP to the corresponding nucleoside 5' monophosphate, but has higher affinity for cAMP, and is more efficient with cAMP as substrate. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Dec 2011]

PDE10A Gene-Disease associations (from GenCC):

• striatal degeneration, autosomal dominant 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• dyskinesia, limb and orofacial, infantile-onset

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Ambry Genetics
• infantile-onset generalized dyskinesia with orofacial involvement

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• childhood-onset benign chorea with striatal involvement

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385079.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE10A	NM_001385079.1	MANE Select	c.994+8377C>T		intron	N/A	NP_001372008.1
	PDE10A	NM_001130690.3		c.196+8377C>T		intron	N/A	NP_001124162.1
	PDE10A	NM_006661.4		c.166+8377C>T		intron	N/A	NP_006652.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE10A	ENST00000539869.4	TSL:1 MANE Select	c.994+8377C>T		intron	N/A	ENSP00000438284.3
	PDE10A	ENST00000647768.3		c.370+8377C>T		intron	N/A	ENSP00000497930.3
	PDE10A	ENST00000672902.1		c.247+8377C>T		intron	N/A	ENSP00000500351.1

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105060 AN: 151726 Hom.: 39649 Cov.: 31

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.919

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.828

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.864

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.713

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

GnomAD4 genome AF: 0.692 AC: 105112 AN: 151842 Hom.: 39665 Cov.: 31 AF XY: 0.695 AC XY: 51553 AN XY: 74228

African (AFR) AF: 0.364 AC: 15046 AN: 41386

American (AMR) AF: 0.764 AC: 11639 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.828 AC: 2872 AN: 3468

East Asian (EAS) AF: 0.695 AC: 3590 AN: 5168

South Asian (SAS) AF: 0.799 AC: 3845 AN: 4814

European-Finnish (FIN) AF: 0.864 AC: 9150 AN: 10596

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.831 AC: 56410 AN: 67850

Other (OTH) AF: 0.711 AC: 1502 AN: 2112

Alfa AF: 0.737 Hom.: 7582

Bravo AF: 0.668

Asia WGS AF: 0.712 AC: 2469 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.49
PhyloP100		-0.67

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: rs484594; hg19: chr6-165948551;