6-165627133-A-T

Position:

• chr6-165627133-A-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+34814T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 152,054 control chromosomes in the GnomAD database, including 23,543 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 0.54 (23543 hom., cov: 32)
• Consequence: PDE10A NM_001385079.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE10A	NM_001385079.1	c.865+34814T>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+34814T>A		intron_variant		1	NM_001385079.1	ENSP00000438284.3

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81638 AN: 151938 Hom.: 23518 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.537 AC: 81700 AN: 152054 Hom.: 23543 Cov.: 32 AF XY: 0.542 AC XY: 40244 AN XY: 74310

Gnomad4 AFR AF: 0.325

Gnomad4 AMR AF: 0.651

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.727

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.655

Gnomad4 NFE AF: 0.615

Gnomad4 OTH AF: 0.533

Alfa AF: 0.583 Hom.: 3359

Bravo AF: 0.533

Asia WGS AF: 0.538 AC: 1869 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	0.081
DANN	Benign	0.45

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: rs4709082; hg19: chr6-166040621;