rs9347083

Variant names:

• chr6-165641082-C-A
• rs9347083
• NM_001385079.1:c.865+20865G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-165641082-C-A
• chr6-165641082-C-G

Variant summary

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

The NM_001385079.1(PDE10A):​c.865+20865G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,106 control chromosomes in the GnomAD database, including 5,071 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 0.22 (5071 hom., cov: 33)
• Consequence: PDE10A NM_001385079.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.713
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE10A	NM_001385079.1	c.865+20865G>T		intron_variant	Intron 1 of 21	ENST00000539869.4	NP_001372008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE10A	ENST00000539869.4	c.865+20865G>T		intron_variant	Intron 1 of 21	1	NM_001385079.1	ENSP00000438284.3

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33899 AN: 151988 Hom.: 5055 Cov.: 33

Gnomad AFR AF: 0.0531

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.223 AC: 33928 AN: 152106 Hom.: 5071 Cov.: 33 AF XY: 0.229 AC XY: 17037 AN XY: 74344

African (AFR) AF: 0.0529 AC: 2199 AN: 41538

American (AMR) AF: 0.378 AC: 5781 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 635 AN: 3464

East Asian (EAS) AF: 0.370 AC: 1914 AN: 5166

South Asian (SAS) AF: 0.143 AC: 691 AN: 4820

European-Finnish (FIN) AF: 0.347 AC: 3662 AN: 10560

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18426 AN: 67962

Other (OTH) AF: 0.200 AC: 421 AN: 2110

Alfa AF: 0.248 Hom.: 9811

Bravo AF: 0.222

Asia WGS AF: 0.248 AC: 865 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	0.24
DANN	Benign	0.77
PhyloP100		-0.71

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: rs9347083; hg19: chr6-166054570;