PDE10A p.Ala564Ala

Variant names:

• chr6-165418738-G-G
• NM_001385079.1:c.

Your query was ambiguous. Multiple possible variants found:

• chr6-165418739--
• chr6-165418739-C-A
• chr6-165418739-C-G
• chr6-165418739-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001385079.1(PDE10A):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDE10A NM_001385079.1 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.744
• Publications: 0 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: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• dyskinesia, limb and orofacial, infantile-onset

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Genomics England PanelApp
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE10A	NM_001385079.1	MANE Select	c.		exon_region	Exon 11 of 22	NP_001372008.1	Q9Y233-3
	PDE10A	NM_001130690.3		c.		exon_region	Exon 11 of 22	NP_001124162.1	Q9Y233-2
	PDE10A	NM_006661.4		c.		exon_region	Exon 12 of 23	NP_006652.1	A0A1B1UZR0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE10A	ENST00000539869.4	TSL:1 MANE Select	c.		exon_region	Exon 11 of 22	ENSP00000438284.3	Q9Y233-3
	PDE10A	ENST00000647768.3		c.		exon_region	Exon 12 of 23	ENSP00000497930.3	A0A3B3ITT8
	PDE10A	ENST00000672902.1		c.		exon_region	Exon 12 of 23	ENSP00000500351.1	A0A5F9ZHF9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.74

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-165832226;