rs1039002

Variant names:

• chr6-165741969-G-A
• rs1039002
• ENST00000647768.3:c.107-30816C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-165741969-G-A
• chr6-165741969-G-C
• chr6-165741969-G-T

Variant summary

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

The ENST00000647768.3(PDE10A):​c.107-30816C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0592 in 152,228 control chromosomes in the GnomAD database, including 488 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 0.059 (488 hom., cov: 32)
• Consequence: PDE10A ENST00000647768.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.431
• Publications: 19 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE10A	XM_011535387.4	c.59-30816C>T		intron_variant	Intron 2 of 23		XP_011533689.2
PDE10A	XM_017010194.3	c.59-30816C>T		intron_variant	Intron 2 of 23		XP_016865683.1
PDE10A	XM_017010197.3	c.59-30816C>T		intron_variant	Intron 2 of 18		XP_016865686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE10A	ENST00000647768.3	c.107-30816C>T		intron_variant	Intron 1 of 22			ENSP00000497930.3
PDE10A	ENST00000672902.1	c.-17-30816C>T		intron_variant	Intron 1 of 22			ENSP00000500351.1
PDE10A	ENST00000672859.1	c.-17-30816C>T		intron_variant	Intron 3 of 24			ENSP00000500900.1

Frequencies

GnomAD3 genomes AF: 0.0591 AC: 8997 AN: 152110 Hom.: 484 Cov.: 32

Gnomad AFR AF: 0.0122

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.0294

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.0506

Gnomad FIN AF: 0.0966

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0559

Gnomad OTH AF: 0.0512

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

GnomAD4 genome AF: 0.0592 AC: 9006 AN: 152228 Hom.: 488 Cov.: 32 AF XY: 0.0639 AC XY: 4754 AN XY: 74412

African (AFR) AF: 0.0122 AC: 507 AN: 41560

American (AMR) AF: 0.168 AC: 2571 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0294 AC: 102 AN: 3466

East Asian (EAS) AF: 0.124 AC: 642 AN: 5174

South Asian (SAS) AF: 0.0500 AC: 241 AN: 4818

European-Finnish (FIN) AF: 0.0966 AC: 1023 AN: 10588

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0559 AC: 3801 AN: 68014

Other (OTH) AF: 0.0507 AC: 107 AN: 2112

Alfa AF: 0.0585 Hom.: 1484

Bravo AF: 0.0644

Asia WGS AF: 0.0730 AC: 255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.68
PhyloP100		0.43

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1039002; hg19: chr6-166155457;