rs9459417

Variant names:

• chr6-165424504-T-C
• rs9459417
• NM_001385079.1:c.1653+4154A>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.1653+4154A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,222 control chromosomes in the GnomAD database, including 1,058 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 0.12 (1058 hom., cov: 32)
• Consequence: PDE10A NM_001385079.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.993
• Publications: 4 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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE10A	NM_001385079.1	c.1653+4154A>G		intron_variant	Intron 10 of 21	ENST00000539869.4	NP_001372008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE10A	ENST00000539869.4	c.1653+4154A>G		intron_variant	Intron 10 of 21	1	NM_001385079.1	ENSP00000438284.3

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17536 AN: 152104 Hom.: 1052 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.0635

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.0456

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.115 AC: 17573 AN: 152222 Hom.: 1058 Cov.: 32 AF XY: 0.112 AC XY: 8367 AN XY: 74438

African (AFR) AF: 0.127 AC: 5285 AN: 41550

American (AMR) AF: 0.107 AC: 1636 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 665 AN: 3470

East Asian (EAS) AF: 0.0638 AC: 330 AN: 5172

South Asian (SAS) AF: 0.145 AC: 701 AN: 4820

European-Finnish (FIN) AF: 0.0456 AC: 484 AN: 10612

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8084 AN: 67986

Other (OTH) AF: 0.132 AC: 280 AN: 2114

Alfa AF: 0.123 Hom.: 3624

Bravo AF: 0.121

Asia WGS AF: 0.123 AC: 425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.42
DANN	Benign	0.59
PhyloP100		-0.99

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: rs9459417; hg19: chr6-165837992; COSMIC: COSV63093583;