6-165635380-G-A

Variant names:

• chr6-165635380-G-A
• rs9459465
• NM_001385079.1:c.865+26567C>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+26567C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,132 control chromosomes in the GnomAD database, including 2,806 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 0.18 (2806 hom., cov: 32)
• Consequence: PDE10A NM_001385079.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75
• Publications: 3 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 (NFE) allele frequency at 95% confidence interval = 0.226 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE10A	NM_001385079.1	MANE Select	c.865+26567C>T		intron	N/A	NP_001372008.1
	PDE10A	NM_001130690.3		c.67+26567C>T		intron	N/A	NP_001124162.1
	PDE10A	NM_006661.4		c.-92+26567C>T		intron	N/A	NP_006652.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE10A	ENST00000539869.4	TSL:1 MANE Select	c.865+26567C>T		intron	N/A	ENSP00000438284.3
	PDE10A	ENST00000647768.3		c.241+75639C>T		intron	N/A	ENSP00000497930.3
	PDE10A	ENST00000672902.1		c.118+75639C>T		intron	N/A	ENSP00000500351.1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27496 AN: 152014 Hom.: 2805 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.0179

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.181 AC: 27504 AN: 152132 Hom.: 2806 Cov.: 32 AF XY: 0.176 AC XY: 13107 AN XY: 74368

African (AFR) AF: 0.121 AC: 5041 AN: 41518

American (AMR) AF: 0.170 AC: 2603 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 885 AN: 3470

East Asian (EAS) AF: 0.0179 AC: 93 AN: 5184

South Asian (SAS) AF: 0.151 AC: 728 AN: 4818

European-Finnish (FIN) AF: 0.184 AC: 1950 AN: 10576

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15580 AN: 67972

Other (OTH) AF: 0.198 AC: 418 AN: 2112

Alfa AF: 0.214 Hom.: 15790

Bravo AF: 0.178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0060
DANN	Benign	0.22
PhyloP100		-1.8

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: rs9459465; hg19: chr6-166048868;