chr6-165430823-T-C

Position:

• chr6-165430823-T-C

Variant summary

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

The NM_001385079.1(PDE10A):​c.1543-478A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 151,888 control chromosomes in the GnomAD database, including 39,833 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 0.72 (39833 hom., cov: 31)
• Consequence: PDE10A NM_001385079.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.901

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE10A	NM_001385079.1	c.1543-478A>G		intron_variant		ENST00000539869.4	NP_001372008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE10A	ENST00000539869.4	c.1543-478A>G		intron_variant		1	NM_001385079.1	ENSP00000438284.3

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109659 AN: 151770 Hom.: 39780 Cov.: 31

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.892

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.746

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

GnomAD4 genome AF: 0.723 AC: 109772 AN: 151888 Hom.: 39833 Cov.: 31 AF XY: 0.723 AC XY: 53634 AN XY: 74232

Gnomad4 AFR AF: 0.787

Gnomad4 AMR AF: 0.707

Gnomad4 ASJ AF: 0.796

Gnomad4 EAS AF: 0.578

Gnomad4 SAS AF: 0.724

Gnomad4 FIN AF: 0.684

Gnomad4 NFE AF: 0.697

Gnomad4 OTH AF: 0.741

Alfa AF: 0.704 Hom.: 46800

Bravo AF: 0.725

Asia WGS AF: 0.646 AC: 2246 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.2
DANN	Benign	0.43

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: rs470922; hg19: chr6-165844311;