6-165785528-C-T

Variant names:

• chr6-165785528-C-T
• rs9347088
• ENST00000647768.3:c.107-74375G>A

Variant summary

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

The ENST00000647768.3(PDE10A):​c.107-74375G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 151,996 control chromosomes in the GnomAD database, including 24,630 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 0.57 (24630 hom., cov: 33)
• Consequence: PDE10A ENST00000647768.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 2 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE10A	XM_011535387.4	c.59-74375G>A		intron_variant	Intron 2 of 23		XP_011533689.2
PDE10A	XM_017010194.3	c.59-74375G>A		intron_variant	Intron 2 of 23		XP_016865683.1
PDE10A	XM_017010197.3	c.59-74375G>A		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.107-74375G>A		intron_variant	Intron 1 of 22			ENSP00000497930.3
PDE10A	ENST00000672902.1	c.-17-74375G>A		intron_variant	Intron 1 of 22			ENSP00000500351.1
PDE10A	ENST00000672859.1	c.-18+6383G>A		intron_variant	Intron 3 of 24			ENSP00000500900.1

Frequencies

GnomAD3 genomes AF: 0.567 AC: 86183 AN: 151878 Hom.: 24611 Cov.: 33

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.578

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

GnomAD4 genome AF: 0.567 AC: 86249 AN: 151996 Hom.: 24630 Cov.: 33 AF XY: 0.563 AC XY: 41797 AN XY: 74298

African (AFR) AF: 0.597 AC: 24727 AN: 41442

American (AMR) AF: 0.556 AC: 8499 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1934 AN: 3466

East Asian (EAS) AF: 0.355 AC: 1837 AN: 5172

South Asian (SAS) AF: 0.432 AC: 2082 AN: 4822

European-Finnish (FIN) AF: 0.558 AC: 5890 AN: 10548

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39310 AN: 67952

Other (OTH) AF: 0.574 AC: 1214 AN: 2114

Alfa AF: 0.501 Hom.: 2565

Bravo AF: 0.574

Asia WGS AF: 0.395 AC: 1375 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.80
DANN	Benign	0.28
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs9347088; hg19: chr6-166199016;