rs9364813

Variant names:

• chr6-165715150-G-A
• rs9364813
• ENST00000647768.3:c.107-3997C>T

Variant summary

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

The ENST00000647768.3(PDE10A):​c.107-3997C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0946 in 152,236 control chromosomes in the GnomAD database, including 971 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 0.095 (971 hom., cov: 33)
• Consequence: PDE10A ENST00000647768.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.888
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE10A	XM_011535387.4	c.59-3997C>T		intron_variant	Intron 2 of 23		XP_011533689.2
PDE10A	XM_017010194.3	c.59-3997C>T		intron_variant	Intron 2 of 23		XP_016865683.1
PDE10A	XM_017010197.3	c.59-3997C>T		intron_variant	Intron 2 of 18		XP_016865686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE10A	ENST00000647768.3	c.107-3997C>T		intron_variant	Intron 1 of 22			ENSP00000497930.3
PDE10A	ENST00000672902.1	c.-17-3997C>T		intron_variant	Intron 1 of 22			ENSP00000500351.1
PDE10A	ENST00000672859.1	c.-17-3997C>T		intron_variant	Intron 3 of 24			ENSP00000500900.1

Frequencies

GnomAD3 genomes AF: 0.0947 AC: 14400 AN: 152118 Hom.: 971 Cov.: 33

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.0758

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.0317

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.0519

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.0946 AC: 14407 AN: 152236 Hom.: 971 Cov.: 33 AF XY: 0.0968 AC XY: 7206 AN XY: 74442

African (AFR) AF: 0.153 AC: 6367 AN: 41528

American (AMR) AF: 0.0757 AC: 1159 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 413 AN: 3472

East Asian (EAS) AF: 0.234 AC: 1206 AN: 5160

South Asian (SAS) AF: 0.223 AC: 1075 AN: 4824

European-Finnish (FIN) AF: 0.0317 AC: 337 AN: 10616

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0519 AC: 3529 AN: 68016

Other (OTH) AF: 0.105 AC: 221 AN: 2112

Alfa AF: 0.0675 Hom.: 988

Bravo AF: 0.0971

Asia WGS AF: 0.215 AC: 744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.9
DANN	Benign	0.82
PhyloP100		0.89

Splicing

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

Other links and lift over

dbSNP: rs9364813; hg19: chr6-166128638;