6-165418739-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001385079.1(PDE10A):c.1692G>A(p.Ala564=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,611,826 control chromosomes in the GnomAD database, including 61,850 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7296 hom., cov: 32)
  • Exomes 𝑓: 0.27 (54554 hom.)
• Consequence: PDE10A NM_001385079.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.744

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 6-165418739-C-T is Benign according to our data. Variant chr6-165418739-C-T is described in ClinVar as [Benign]. Clinvar id is 1164211.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.744 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE10A	NM_001385079.1	c.1692G>A	p.Ala564=	synonymous_variant	11/22	ENST00000539869.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE10A	ENST00000539869.4	c.1692G>A	p.Ala564=	synonymous_variant	11/22	1	NM_001385079.1	P3

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45439 AN: 151782 Hom.: 7289 Cov.: 32

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.0913

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.310

GnomAD3 exomes AF: 0.252 AC: 63168 AN: 250980 Hom.: 8966 AF XY: 0.255 AC XY: 34574 AN XY: 135676

Gnomad AFR exome AF: 0.407

Gnomad AMR exome AF: 0.148

Gnomad ASJ exome AF: 0.390

Gnomad EAS exome AF: 0.0954

Gnomad SAS exome AF: 0.215

Gnomad FIN exome AF: 0.232

Gnomad NFE exome AF: 0.287

Gnomad OTH exome AF: 0.273

GnomAD4 exome AF: 0.267 AC: 389863 AN: 1459926 Hom.: 54554 Cov.: 32 AF XY: 0.266 AC XY: 193558 AN XY: 726388

Gnomad4 AFR exome AF: 0.414

Gnomad4 AMR exome AF: 0.158

Gnomad4 ASJ exome AF: 0.388

Gnomad4 EAS exome AF: 0.0856

Gnomad4 SAS exome AF: 0.214

Gnomad4 FIN exome AF: 0.229

Gnomad4 NFE exome AF: 0.275

Gnomad4 OTH exome AF: 0.279

GnomAD4 genome AF: 0.299 AC: 45475 AN: 151900 Hom.: 7296 Cov.: 32 AF XY: 0.295 AC XY: 21898 AN XY: 74226

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.0919

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.313

Alfa AF: 0.285 Hom.: 10887

Bravo AF: 0.305

Asia WGS AF: 0.185 AC: 643 AN: 3478

EpiCase AF: 0.301

EpiControl AF: 0.311

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Striatal degeneration, autosomal dominant 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Infantile-onset generalized dyskinesia with orofacial involvement Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
Cadd	Benign	6.8
Dann	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs220740; hg19: chr6-165832227; COSMIC: COSV63097189;