6-165626591-C-T

Position:

• chr6-165626591-C-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+35356G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.854 in 152,276 control chromosomes in the GnomAD database, including 55,612 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 0.85 (55612 hom., cov: 33)
• Consequence: PDE10A NM_001385079.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37

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 (EAS) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE10A	NM_001385079.1	c.865+35356G>A		intron_variant		ENST00000539869.4	NP_001372008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE10A	ENST00000539869.4	c.865+35356G>A		intron_variant		1	NM_001385079.1	ENSP00000438284	P3

Frequencies

GnomAD3 genomes AF: 0.854 AC: 129955 AN: 152158 Hom.: 55559 Cov.: 33

Gnomad AFR AF: 0.828

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.885

Gnomad ASJ AF: 0.879

Gnomad EAS AF: 0.887

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.879

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.864

Gnomad OTH AF: 0.853

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

GnomAD4 genome AF: 0.854 AC: 130068 AN: 152276 Hom.: 55612 Cov.: 33 AF XY: 0.856 AC XY: 63746 AN XY: 74438

Gnomad4 AFR AF: 0.828

Gnomad4 AMR AF: 0.885

Gnomad4 ASJ AF: 0.879

Gnomad4 EAS AF: 0.888

Gnomad4 SAS AF: 0.744

Gnomad4 FIN AF: 0.879

Gnomad4 NFE AF: 0.864

Gnomad4 OTH AF: 0.855

Alfa AF: 0.859 Hom.: 25588

Bravo AF: 0.858

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.085
DANN	Benign	0.71

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: rs1033700; hg19: chr6-166040079; COSMIC: COSV64831634;