Genetic Variant PDE10A:c.107-59562G>A (chr6-165770715-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000647768.3(PDE10A):c.107-59562G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,170 control chromosomes in the GnomAD database, including 2,604 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 0.16 ( 2604 hom., cov: 32)

Consequence

PDE10A
ENST00000647768.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.983

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

striatal degeneration, autosomal dominant 2
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
dyskinesia, limb and orofacial, infantile-onset
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Ambry Genetics
infantile-onset generalized dyskinesia with orofacial involvement
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
childhood-onset benign chorea with striatal involvement
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PDE10A links:

ENSG00000236627 (HGNC:):

ENSG00000236627 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
PDE10A	XM_011535387.4 link	c.59-59562G>A	intron_variant	Intron 2 of 23	XP_011533689.2
PDE10A	XM_017010194.3 link	c.59-59562G>A	intron_variant	Intron 2 of 23	XP_016865683.1
PDE10A	XM_017010197.3 link	c.59-59562G>A	intron_variant	Intron 2 of 18	XP_016865686.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
PDE10A	ENST00000647768.3 link	c.107-59562G>A	intron_variant	Intron 1 of 22	ENSP00000497930.3
PDE10A	ENST00000672902.1 link	c.-17-59562G>A	intron_variant	Intron 1 of 22	ENSP00000500351.1
PDE10A	ENST00000672859.1 link	c.-18+21196G>A	intron_variant	Intron 3 of 24	ENSP00000500900.1

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

24488

AN:

152052

Hom.:

2600

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0665

Gnomad AMI

AF:

0.271

Gnomad AMR

AF:

0.192

Gnomad ASJ

AF:

0.112

Gnomad EAS

AF:

0.451

Gnomad SAS

AF:

0.317

Gnomad FIN

AF:

0.243

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.167

Gnomad OTH

AF:

0.149

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

GnomAD4 genome

AF:

0.161

AC:

24496

AN:

152170

Hom.:

2604

Cov.:

AF XY:

0.170

AC XY:

12664

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0665

AC:

2764

AN:

41540

American (AMR)

AF:

0.192

AC:

2938

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.112

AC:

388

AN:

3462

East Asian (EAS)

AF:

0.450

AC:

2329

AN:

5174

South Asian (SAS)

AF:

0.315

AC:

1514

AN:

4800

European-Finnish (FIN)

AF:

0.243

AC:

2571

AN:

10580

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.167

AC:

11383

AN:

68002

Other (OTH)

AF:

0.155

AC:

326

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

986

1973

2959

3946

4932

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

264

528

792

1056

1320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.163

Hom.:

9659

Bravo

AF:

0.149

Asia WGS

AF:

0.357

AC:

1239

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.79

(source)

DANN

Benign

0.75

PhyloP100

-0.98

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over