rs12528870

chr6-165783788-G-Achr6-165783788-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PDE10A	XM_011535387.4	c.59-72635C>T		intron_variant
PDE10A	XM_017010194.3	c.59-72635C>T		intron_variant
PDE10A	XM_017010197.3	c.59-72635C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE10A	ENST00000366882.7	c.-615+203741C>T		intron_variant		5
PDE10A	ENST00000647768.3	c.107-72635C>T		intron_variant				A2
PDE10A	ENST00000672859.1	c.-18+8123C>T		intron_variant				A2

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

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.0746

Gnomad4 ASJ AF: 0.0279

Gnomad4 EAS AF: 0.214

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.0718

Gnomad4 NFE AF: 0.0389

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0543 Hom.: 762

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12528870; hg19: chr6-166197276;