chr6-165430823-T-C

Variant names:

• chr6-165430823-T-C
• rs470922
• NM_001385079.1:c.1543-478A>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.1543-478A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 151,888 control chromosomes in the GnomAD database, including 39,833 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 0.72 (39833 hom., cov: 31)
• Consequence: PDE10A NM_001385079.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.901
• 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: 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.78 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.1543-478A>G		intron	N/A	NP_001372008.1	Q9Y233-3
	PDE10A	NM_001130690.3		c.745-478A>G		intron	N/A	NP_001124162.1	Q9Y233-2
	PDE10A	NM_006661.4		c.715-478A>G		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.1543-478A>G		intron	N/A	ENSP00000438284.3	Q9Y233-3
	PDE10A	ENST00000647768.3		c.919-478A>G		intron	N/A	ENSP00000497930.3	A0A3B3ITT8
	PDE10A	ENST00000672902.1		c.796-478A>G		intron	N/A	ENSP00000500351.1	A0A5F9ZHF9

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109659 AN: 151770 Hom.: 39780 Cov.: 31

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.892

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.746

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

GnomAD4 genome AF: 0.723 AC: 109772 AN: 151888 Hom.: 39833 Cov.: 31 AF XY: 0.723 AC XY: 53634 AN XY: 74232

African (AFR) AF: 0.787 AC: 32591 AN: 41428

American (AMR) AF: 0.707 AC: 10778 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 2762 AN: 3468

East Asian (EAS) AF: 0.578 AC: 2988 AN: 5168

South Asian (SAS) AF: 0.724 AC: 3486 AN: 4818

European-Finnish (FIN) AF: 0.684 AC: 7209 AN: 10536

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.697 AC: 47332 AN: 67906

Other (OTH) AF: 0.741 AC: 1563 AN: 2110

Alfa AF: 0.705 Hom.: 53757

Bravo AF: 0.725

Asia WGS AF: 0.646 AC: 2246 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.2
DANN	Benign	0.43
PhyloP100		-0.90

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: rs470922; hg19: chr6-165844311;