6-165755520-G-T

Variant names:

• chr6-165755520-G-T
• rs1546141
• ENST00000647768.3:c.107-44367C>A

Variant summary

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

The ENST00000647768.3(PDE10A):​c.107-44367C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,018 control chromosomes in the GnomAD database, including 2,661 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 0.17 (2661 hom., cov: 32)
• Consequence: PDE10A ENST00000647768.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820
• Publications: 1 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

ENSG00000236627 (HGNC:):

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 = 0.349 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000647768.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE10A	ENST00000647768.3		c.107-44367C>A		intron	N/A	ENSP00000497930.3
	PDE10A	ENST00000672902.1		c.-17-44367C>A		intron	N/A	ENSP00000500351.1
	PDE10A	ENST00000672859.1		c.-18+36391C>A		intron	N/A	ENSP00000500900.1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26486 AN: 151900 Hom.: 2651 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.0640

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.174 AC: 26519 AN: 152018 Hom.: 2661 Cov.: 32 AF XY: 0.179 AC XY: 13333 AN XY: 74322

African (AFR) AF: 0.235 AC: 9735 AN: 41438

American (AMR) AF: 0.164 AC: 2513 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0640 AC: 222 AN: 3470

East Asian (EAS) AF: 0.363 AC: 1873 AN: 5158

South Asian (SAS) AF: 0.135 AC: 650 AN: 4820

European-Finnish (FIN) AF: 0.232 AC: 2453 AN: 10552

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8540 AN: 67990

Other (OTH) AF: 0.138 AC: 292 AN: 2110

Alfa AF: 0.111 Hom.: 251

Bravo AF: 0.174

Asia WGS AF: 0.238 AC: 827 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.77
DANN	Benign	0.47
PhyloP100		0.082

Splicing

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

Other links and lift over

dbSNP: rs1546141; hg19: chr6-166169008;