6-165521933-A-G

Variant names:

• chr6-165521933-A-G
• rs519595
• NM_001385079.1:c.994+21507T>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.994+21507T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 152,170 control chromosomes in the GnomAD database, including 49,548 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 0.80 (49548 hom., cov: 33)
• Consequence: PDE10A NM_001385079.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• 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: 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=-1.07).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.858 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.994+21507T>C		intron	N/A	NP_001372008.1
	PDE10A	NM_001130690.3		c.196+21507T>C		intron	N/A	NP_001124162.1
	PDE10A	NM_006661.4		c.166+21507T>C		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.994+21507T>C		intron	N/A	ENSP00000438284.3
	PDE10A	ENST00000647768.3		c.370+21507T>C		intron	N/A	ENSP00000497930.3
	PDE10A	ENST00000672902.1		c.247+21507T>C		intron	N/A	ENSP00000500351.1

Frequencies

GnomAD3 genomes AF: 0.803 AC: 122039 AN: 152052 Hom.: 49523 Cov.: 33

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.868

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.840

Gnomad FIN AF: 0.904

Gnomad MID AF: 0.790

Gnomad NFE AF: 0.864

Gnomad OTH AF: 0.800

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

GnomAD4 genome AF: 0.802 AC: 122116 AN: 152170 Hom.: 49548 Cov.: 33 AF XY: 0.803 AC XY: 59716 AN XY: 74388

African (AFR) AF: 0.686 AC: 28445 AN: 41488

American (AMR) AF: 0.742 AC: 11330 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.868 AC: 3014 AN: 3472

East Asian (EAS) AF: 0.811 AC: 4195 AN: 5172

South Asian (SAS) AF: 0.841 AC: 4061 AN: 4830

European-Finnish (FIN) AF: 0.904 AC: 9598 AN: 10614

Middle Eastern (MID) AF: 0.795 AC: 232 AN: 292

European-Non Finnish (NFE) AF: 0.864 AC: 58764 AN: 68010

Other (OTH) AF: 0.798 AC: 1684 AN: 2110

Alfa AF: 0.835 Hom.: 81804

Bravo AF: 0.785

Asia WGS AF: 0.798 AC: 2772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.57
DANN	Benign	0.22
PhyloP100		-1.5

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: rs519595; hg19: chr6-165935421;