6-165638020-G-T

Variant names:

• chr6-165638020-G-T
• rs2983516
• NM_001385079.1:c.865+23927C>A

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+23927C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 151,810 control chromosomes in the GnomAD database, including 3,723 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 0.22 (3723 hom., cov: 32)
• Consequence: PDE10A NM_001385079.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.407
• 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.229 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE10A	NM_001385079.1	MANE Select	c.865+23927C>A		intron	N/A	NP_001372008.1
	PDE10A	NM_001130690.3		c.67+23927C>A		intron	N/A	NP_001124162.1
	PDE10A	NM_006661.4		c.-92+23927C>A		intron	N/A	NP_006652.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE10A	ENST00000539869.4	TSL:1 MANE Select	c.865+23927C>A		intron	N/A	ENSP00000438284.3
	PDE10A	ENST00000647768.3		c.241+72999C>A		intron	N/A	ENSP00000497930.3
	PDE10A	ENST00000672902.1		c.118+72999C>A		intron	N/A	ENSP00000500351.1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32870 AN: 151694 Hom.: 3722 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.00618

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.217 AC: 32877 AN: 151810 Hom.: 3723 Cov.: 32 AF XY: 0.216 AC XY: 16011 AN XY: 74186

African (AFR) AF: 0.219 AC: 9054 AN: 41368

American (AMR) AF: 0.189 AC: 2877 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 988 AN: 3472

East Asian (EAS) AF: 0.00619 AC: 32 AN: 5166

South Asian (SAS) AF: 0.213 AC: 1025 AN: 4816

European-Finnish (FIN) AF: 0.215 AC: 2259 AN: 10514

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15772 AN: 67922

Other (OTH) AF: 0.243 AC: 511 AN: 2106

Alfa AF: 0.227 Hom.: 17043

Bravo AF: 0.215

Asia WGS AF: 0.124 AC: 430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.63
DANN	Benign	0.67
PhyloP100		-0.41

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: rs2983516; hg19: chr6-166051508; COSMIC: COSV64840526;