chr6-165648891-T-C

Position:

• chr6-165648891-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.865+13056A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 152,038 control chromosomes in the GnomAD database, including 7,775 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 0.32 (7775 hom., cov: 32)
• Consequence: PDE10A NM_001385079.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE10A	NM_001385079.1	c.865+13056A>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.865+13056A>G		intron_variant		1	NM_001385079.1	ENSP00000438284	P3

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48214 AN: 151922 Hom.: 7767 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.317 AC: 48244 AN: 152038 Hom.: 7775 Cov.: 32 AF XY: 0.313 AC XY: 23264 AN XY: 74314

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.310

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.332

Alfa AF: 0.321 Hom.: 11074

Bravo AF: 0.323

Asia WGS AF: 0.314 AC: 1089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.70
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9365899; hg19: chr6-166062379;