rs1039002

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.89).
• 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/exons	MANE	Protein	UniProt
PDE10A	XM_011535387.4	c.59-30816C>T		intron_variant			XP_011533689.2
PDE10A	XM_017010194.3	c.59-30816C>T		intron_variant			XP_016865683.1
PDE10A	XM_017010197.3	c.59-30816C>T		intron_variant			XP_016865686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE10A	ENST00000366882.7	c.-614-198401C>T		intron_variant		5		ENSP00000355847
PDE10A	ENST00000647768.3	c.107-30816C>T		intron_variant				ENSP00000497930	A2
PDE10A	ENST00000672859.1	c.-17-30816C>T		intron_variant				ENSP00000500900	A2

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

Gnomad4 AFR AF: 0.0122

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.0294

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.0500

Gnomad4 FIN AF: 0.0966

Gnomad4 NFE AF: 0.0559

Gnomad4 OTH AF: 0.0507

Alfa AF: 0.0575 Hom.: 653

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1039002; hg19: chr6-166155457;