NM_001385079.1:c.995-9460T>G

Variant names:

• chr6-165491803-A-C
• rs650490
• NM_001385079.1:c.995-9460T>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.995-9460T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 151,368 control chromosomes in the GnomAD database, including 6,629 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 0.29 (6629 hom., cov: 31)
• Consequence: PDE10A NM_001385079.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.316
• Publications: 1 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE10A	NM_001385079.1	c.995-9460T>G		intron_variant	Intron 2 of 21	ENST00000539869.4	NP_001372008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE10A	ENST00000539869.4	c.995-9460T>G		intron_variant	Intron 2 of 21	1	NM_001385079.1	ENSP00000438284.3

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43640 AN: 151250 Hom.: 6610 Cov.: 31

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.289 AC: 43706 AN: 151368 Hom.: 6629 Cov.: 31 AF XY: 0.287 AC XY: 21257 AN XY: 73950

African (AFR) AF: 0.387 AC: 15924 AN: 41140

American (AMR) AF: 0.274 AC: 4170 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 856 AN: 3462

East Asian (EAS) AF: 0.288 AC: 1482 AN: 5146

South Asian (SAS) AF: 0.276 AC: 1321 AN: 4792

European-Finnish (FIN) AF: 0.212 AC: 2222 AN: 10498

Middle Eastern (MID) AF: 0.284 AC: 83 AN: 292

European-Non Finnish (NFE) AF: 0.248 AC: 16818 AN: 67808

Other (OTH) AF: 0.280 AC: 588 AN: 2100

Alfa AF: 0.289 Hom.: 719

Bravo AF: 0.297

Asia WGS AF: 0.297 AC: 1033 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.5
DANN	Benign	0.90
PhyloP100		0.32

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: rs650490; hg19: chr6-165905291;