rs686406

Variant names:

• chr6-165516665-G-A
• rs686406
• NM_001385079.1:c.994+26775C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001385079.1(PDE10A):​c.994+26775C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 152,072 control chromosomes in the GnomAD database, including 30,813 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 0.59 (30813 hom., cov: 32)
• Consequence: PDE10A NM_001385079.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.360
• Publications: 4 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE10A	NM_001385079.1	c.994+26775C>T		intron_variant	Intron 2 of 21	ENST00000539869.4	NP_001372008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE10A	ENST00000539869.4	c.994+26775C>T		intron_variant	Intron 2 of 21	1	NM_001385079.1	ENSP00000438284.3

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89243 AN: 151954 Hom.: 30810 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.760

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.699

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.683

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.638

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

GnomAD4 genome AF: 0.587 AC: 89263 AN: 152072 Hom.: 30813 Cov.: 32 AF XY: 0.593 AC XY: 44070 AN XY: 74340

African (AFR) AF: 0.194 AC: 8057 AN: 41468

American (AMR) AF: 0.685 AC: 10470 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.760 AC: 2634 AN: 3468

East Asian (EAS) AF: 0.717 AC: 3711 AN: 5174

South Asian (SAS) AF: 0.700 AC: 3380 AN: 4828

European-Finnish (FIN) AF: 0.770 AC: 8138 AN: 10574

Middle Eastern (MID) AF: 0.693 AC: 201 AN: 290

European-Non Finnish (NFE) AF: 0.746 AC: 50676 AN: 67962

Other (OTH) AF: 0.638 AC: 1348 AN: 2112

Alfa AF: 0.700 Hom.: 66748

Bravo AF: 0.565

Asia WGS AF: 0.663 AC: 2301 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.33
DANN	Benign	0.71
PhyloP100		-0.36

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

Other links and lift over

dbSNP: rs686406; hg19: chr6-165930153; COSMIC: COSV63105062;