rs12528870

Variant names:

• chr6-165783788-G-A
• rs12528870
• ENST00000647768.3:c.107-72635C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-165783788-G-A
• chr6-165783788-G-C

Variant summary

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

The ENST00000647768.3(PDE10A):​c.107-72635C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,160 control chromosomes in the GnomAD database, including 2,386 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 0.13 (2386 hom., cov: 32)
• Consequence: PDE10A ENST00000647768.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.683
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE10A	XM_011535387.4	c.59-72635C>T		intron_variant	Intron 2 of 23		XP_011533689.2
PDE10A	XM_017010194.3	c.59-72635C>T		intron_variant	Intron 2 of 23		XP_016865683.1
PDE10A	XM_017010197.3	c.59-72635C>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.107-72635C>T		intron_variant	Intron 1 of 22			ENSP00000497930.3
PDE10A	ENST00000672902.1	c.-17-72635C>T		intron_variant	Intron 1 of 22			ENSP00000500351.1
PDE10A	ENST00000672859.1	c.-18+8123C>T		intron_variant	Intron 3 of 24			ENSP00000500900.1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19773 AN: 152042 Hom.: 2386 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.0742

Gnomad ASJ AF: 0.0279

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0718

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0389

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.130 AC: 19789 AN: 152160 Hom.: 2386 Cov.: 32 AF XY: 0.129 AC XY: 9612 AN XY: 74382

African (AFR) AF: 0.317 AC: 13141 AN: 41460

American (AMR) AF: 0.0746 AC: 1141 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0279 AC: 97 AN: 3472

East Asian (EAS) AF: 0.214 AC: 1105 AN: 5166

South Asian (SAS) AF: 0.109 AC: 527 AN: 4820

European-Finnish (FIN) AF: 0.0718 AC: 761 AN: 10604

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0389 AC: 2647 AN: 68020

Other (OTH) AF: 0.104 AC: 220 AN: 2116

Alfa AF: 0.0718 Hom.: 2602

Bravo AF: 0.139

Asia WGS AF: 0.176 AC: 613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.99
DANN	Benign	0.76
PhyloP100		-0.68

Splicing

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

Other links and lift over

dbSNP: rs12528870; hg19: chr6-166197276;