rs9459465

Positions:

• chr6-165635380-G-A
• chr6-165635380-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE10A	NM_001385079.1	c.865+26567C>T		intron_variant		ENST00000539869.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE10A	ENST00000539869.4	c.865+26567C>T		intron_variant		1	NM_001385079.1	P3

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

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.0179

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.198

Alfa AF: 0.221 Hom.: 8045

Bravo AF: 0.178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs9459465; hg19: chr6-166048868;