rs1033701

Variant names:

• chr6-165627371-G-A
• rs1033701
• NM_001385079.1:c.865+34576C>T

Variant summary

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

The ENST00000539869.4(PDE10A):​c.865+34576C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 151,968 control chromosomes in the GnomAD database, including 6,836 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 (6836 hom., cov: 33)
• Consequence: PDE10A ENST00000539869.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000539869.4. 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+34576C>T		intron	N/A	NP_001372008.1
	PDE10A	NM_001130690.3		c.67+34576C>T		intron	N/A	NP_001124162.1
	PDE10A	NM_006661.4		c.-92+34576C>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+34576C>T		intron	N/A	ENSP00000438284.3
	PDE10A	ENST00000647768.3		c.241+83648C>T		intron	N/A	ENSP00000497930.3
	PDE10A	ENST00000672902.1		c.118+83648C>T		intron	N/A	ENSP00000500351.1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44732 AN: 151850 Hom.: 6822 Cov.: 33

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.295 AC: 44767 AN: 151968 Hom.: 6836 Cov.: 33 AF XY: 0.294 AC XY: 21824 AN XY: 74276

African (AFR) AF: 0.371 AC: 15357 AN: 41438

American (AMR) AF: 0.233 AC: 3566 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1162 AN: 3472

East Asian (EAS) AF: 0.161 AC: 836 AN: 5180

South Asian (SAS) AF: 0.321 AC: 1535 AN: 4788

European-Finnish (FIN) AF: 0.240 AC: 2527 AN: 10530

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18664 AN: 67974

Other (OTH) AF: 0.308 AC: 649 AN: 2104

Alfa AF: 0.292 Hom.: 1006

Bravo AF: 0.296

Asia WGS AF: 0.267 AC: 927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.5
DANN	Benign	0.24
PhyloP100		-0.078

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: rs1033701; hg19: chr6-166040859; COSMIC: COSV64840482;