chr6-165650129-A-G

Variant names:

• chr6-165650129-A-G
• rs3008049
• NM_001385079.1:c.865+11818T>C

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+11818T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 152,072 control chromosomes in the GnomAD database, including 6,121 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 0.28 (6121 hom., cov: 31)
• Consequence: PDE10A NM_001385079.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114
• 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• dyskinesia, limb and orofacial, infantile-onset

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Genomics England PanelApp
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385079.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE10A	NM_001385079.1	MANE Select	c.865+11818T>C		intron	N/A	NP_001372008.1	Q9Y233-3
	PDE10A	NM_001130690.3		c.67+11818T>C		intron	N/A	NP_001124162.1	Q9Y233-2
	PDE10A	NM_006661.4		c.-92+11818T>C		intron	N/A	NP_006652.1	A0A1B1UZR0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE10A	ENST00000539869.4	TSL:1 MANE Select	c.865+11818T>C		intron	N/A	ENSP00000438284.3	Q9Y233-3
	PDE10A	ENST00000647768.3		c.241+60890T>C		intron	N/A	ENSP00000497930.3	A0A3B3ITT8
	PDE10A	ENST00000672902.1		c.118+60890T>C		intron	N/A	ENSP00000500351.1	A0A5F9ZHF9

Frequencies

GnomAD3 genomes AF: 0.276 AC: 42004 AN: 151952 Hom.: 6122 Cov.: 31

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.0220

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.276 AC: 42020 AN: 152072 Hom.: 6121 Cov.: 31 AF XY: 0.273 AC XY: 20285 AN XY: 74314

African (AFR) AF: 0.231 AC: 9595 AN: 41474

American (AMR) AF: 0.250 AC: 3824 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 1295 AN: 3472

East Asian (EAS) AF: 0.0220 AC: 114 AN: 5172

South Asian (SAS) AF: 0.276 AC: 1326 AN: 4806

European-Finnish (FIN) AF: 0.261 AC: 2759 AN: 10564

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21919 AN: 67986

Other (OTH) AF: 0.298 AC: 631 AN: 2116

Alfa AF: 0.306 Hom.: 15987

Bravo AF: 0.274

Asia WGS AF: 0.153 AC: 532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.8
DANN	Benign	0.58
PhyloP100		0.11

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: rs3008049; hg19: chr6-166063617; COSMIC: COSV64840569;