rs9459464

Variant names:

• chr6-165629217-G-A
• rs9459464
• NM_001385079.1:c.865+32730C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-165629217-G-A
• chr6-165629217-G-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.865+32730C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 151,982 control chromosomes in the GnomAD database, including 21,548 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 0.51 (21548 hom., cov: 31)
• Consequence: PDE10A NM_001385079.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE10A	NM_001385079.1	MANE Select	c.865+32730C>T		intron	N/A	NP_001372008.1
	PDE10A	NM_001130690.3		c.67+32730C>T		intron	N/A	NP_001124162.1
	PDE10A	NM_006661.4		c.-92+32730C>T		intron	N/A	NP_006652.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE10A	ENST00000539869.4	TSL:1 MANE Select	c.865+32730C>T		intron	N/A	ENSP00000438284.3
	PDE10A	ENST00000647768.3		c.241+81802C>T		intron	N/A	ENSP00000497930.3
	PDE10A	ENST00000672902.1		c.118+81802C>T		intron	N/A	ENSP00000500351.1

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77448 AN: 151864 Hom.: 21526 Cov.: 31

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.514

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

GnomAD4 genome AF: 0.510 AC: 77505 AN: 151982 Hom.: 21548 Cov.: 31 AF XY: 0.514 AC XY: 38222 AN XY: 74290

African (AFR) AF: 0.286 AC: 11869 AN: 41428

American (AMR) AF: 0.632 AC: 9649 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1904 AN: 3470

East Asian (EAS) AF: 0.726 AC: 3750 AN: 5166

South Asian (SAS) AF: 0.414 AC: 1999 AN: 4828

European-Finnish (FIN) AF: 0.639 AC: 6743 AN: 10556

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.589 AC: 40043 AN: 67956

Other (OTH) AF: 0.512 AC: 1079 AN: 2106

Alfa AF: 0.568 Hom.: 107559

Bravo AF: 0.505

Asia WGS AF: 0.534 AC: 1855 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.28
DANN	Benign	0.87
PhyloP100		-1.4

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: rs9459464; hg19: chr6-166042705;