Variant 6-165418739-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001385079.1(PDE10A):c.1692G>A(p.Ala564Ala) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.744

Variant links:

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 links:

PDE10A (HGNC:):

PDE10A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
PDE10A	NM_001385079.1 linkuse as main transcript	c.1692G>A	p.Ala564Ala	synonymous_variant	11/22	ENST00000539869.4	NP_001372008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE10A	ENST00000539869.4 linkuse as main transcript	c.1692G>A	p.Ala564Ala	synonymous_variant	11/22	1	NM_001385079.1	ENSP00000438284.3		A0A3F2YP58

Frequencies

GnomAD3 genomes

AF:

0.299

AC:

45439

AN:

151782

Hom.:

7289

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.266

AC XY:

193558

AN XY:

726388

show subpopulations

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.:

AF XY:

0.295

AC XY:

21898

AN XY:

74226

show subpopulations

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

LINK: link

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

Labcorp Genetics (formerly Invitae), Labcorp

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over