NM_001385079.1:c.994+8377C>T

Variant names:

• chr6-165535063-G-A
• rs484594
• NM_001385079.1:c.994+8377C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001385079.1(PDE10A):​c.994+8377C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 151,842 control chromosomes in the GnomAD database, including 39,665 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 0.69 (39665 hom., cov: 31)
• Consequence: PDE10A NM_001385079.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.670

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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE10A	NM_001385079.1	c.994+8377C>T		intron_variant	Intron 2 of 21	ENST00000539869.4	NP_001372008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE10A	ENST00000539869.4	c.994+8377C>T		intron_variant	Intron 2 of 21	1	NM_001385079.1	ENSP00000438284.3

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105060 AN: 151726 Hom.: 39649 Cov.: 31

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.919

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.828

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.864

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.713

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

GnomAD4 genome AF: 0.692 AC: 105112 AN: 151842 Hom.: 39665 Cov.: 31 AF XY: 0.695 AC XY: 51553 AN XY: 74228

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.764

Gnomad4 ASJ AF: 0.828

Gnomad4 EAS AF: 0.695

Gnomad4 SAS AF: 0.799

Gnomad4 FIN AF: 0.864

Gnomad4 NFE AF: 0.831

Gnomad4 OTH AF: 0.711

Alfa AF: 0.748 Hom.: 7529

Bravo AF: 0.668

Asia WGS AF: 0.712 AC: 2469 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.49

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: rs484594; hg19: chr6-165948551;