6-165521933-A-G

Position:

• chr6-165521933-A-G

Variant summary

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

The NM_001385079.1(PDE10A):​c.994+21507T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 152,170 control chromosomes in the GnomAD database, including 49,548 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 0.80 (49548 hom., cov: 33)
• Consequence: PDE10A NM_001385079.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51

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]

PDE10A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.07).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE10A	NM_001385079.1	c.994+21507T>C		intron_variant		ENST00000539869.4	NP_001372008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE10A	ENST00000539869.4	c.994+21507T>C		intron_variant		1	NM_001385079.1	ENSP00000438284.3

Frequencies

GnomAD3 genomes AF: 0.803 AC: 122039 AN: 152052 Hom.: 49523 Cov.: 33

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.868

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.840

Gnomad FIN AF: 0.904

Gnomad MID AF: 0.790

Gnomad NFE AF: 0.864

Gnomad OTH AF: 0.800

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

GnomAD4 genome AF: 0.802 AC: 122116 AN: 152170 Hom.: 49548 Cov.: 33 AF XY: 0.803 AC XY: 59716 AN XY: 74388

Gnomad4 AFR AF: 0.686

Gnomad4 AMR AF: 0.742

Gnomad4 ASJ AF: 0.868

Gnomad4 EAS AF: 0.811

Gnomad4 SAS AF: 0.841

Gnomad4 FIN AF: 0.904

Gnomad4 NFE AF: 0.864

Gnomad4 OTH AF: 0.798

Alfa AF: 0.843 Hom.: 49323

Bravo AF: 0.785

Asia WGS AF: 0.798 AC: 2772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.57
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: rs519595; hg19: chr6-165935421;