6-165717956-C-T

Position:

• chr6-165717956-C-T

Variant summary

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

The ENST00000647768.3(PDE10A):​c.107-6803G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 152,074 control chromosomes in the GnomAD database, including 32,683 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 0.65 (32683 hom., cov: 32)
• Consequence: PDE10A ENST00000647768.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.646

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE10A	XM_011535387.4	c.59-6803G>A		intron_variant			XP_011533689.2
PDE10A	XM_017010194.3	c.59-6803G>A		intron_variant			XP_016865683.1
PDE10A	XM_017010197.3	c.59-6803G>A		intron_variant			XP_016865686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE10A	ENST00000647768.3	c.107-6803G>A		intron_variant				ENSP00000497930.3
PDE10A	ENST00000672902.1	c.-17-6803G>A		intron_variant				ENSP00000500351.1
PDE10A	ENST00000672859.1	c.-17-6803G>A		intron_variant				ENSP00000500900.1

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98449 AN: 151956 Hom.: 32652 Cov.: 32

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.672

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.619

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

GnomAD4 genome AF: 0.648 AC: 98520 AN: 152074 Hom.: 32683 Cov.: 32 AF XY: 0.642 AC XY: 47718 AN XY: 74314

Gnomad4 AFR AF: 0.784

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.672

Gnomad4 EAS AF: 0.634

Gnomad4 SAS AF: 0.714

Gnomad4 FIN AF: 0.513

Gnomad4 NFE AF: 0.608

Gnomad4 OTH AF: 0.617

Alfa AF: 0.624 Hom.: 3547

Bravo AF: 0.650

Asia WGS AF: 0.685 AC: 2385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.58

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6919646; hg19: chr6-166131444;