rs9365899

Variant names:

• chr6-165648891-T-C
• rs9365899
• NM_001385079.1:c.865+13056A>G

Variant summary

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

The NM_001385079.1(PDE10A):​c.865+13056A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 152,038 control chromosomes in the GnomAD database, including 7,775 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 0.32 (7775 hom., cov: 32)
• Consequence: PDE10A NM_001385079.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE10A	NM_001385079.1	c.865+13056A>G		intron_variant	Intron 1 of 21	ENST00000539869.4	NP_001372008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE10A	ENST00000539869.4	c.865+13056A>G		intron_variant	Intron 1 of 21	1	NM_001385079.1	ENSP00000438284.3

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48214 AN: 151922 Hom.: 7767 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.317 AC: 48244 AN: 152038 Hom.: 7775 Cov.: 32 AF XY: 0.313 AC XY: 23264 AN XY: 74314

African (AFR) AF: 0.344 AC: 14267 AN: 41466

American (AMR) AF: 0.304 AC: 4649 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1345 AN: 3470

East Asian (EAS) AF: 0.310 AC: 1600 AN: 5168

South Asian (SAS) AF: 0.288 AC: 1386 AN: 4810

European-Finnish (FIN) AF: 0.256 AC: 2705 AN: 10572

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21253 AN: 67970

Other (OTH) AF: 0.332 AC: 697 AN: 2100

Alfa AF: 0.319 Hom.: 15205

Bravo AF: 0.323

Asia WGS AF: 0.314 AC: 1089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.70
DANN	Benign	0.42
PhyloP100		-1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9365899; hg19: chr6-166062379;