6-165355157-C-T

Variant names:

• chr6-165355157-C-T
• rs512584
• NM_001385079.1:c.2784-11655G>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.2784-11655G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 151,878 control chromosomes in the GnomAD database, including 17,314 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 0.47 (17314 hom., cov: 32)
• Consequence: PDE10A NM_001385079.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.116
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE10A	NM_001385079.1	c.2784-11655G>A		intron_variant	Intron 18 of 21	ENST00000539869.4	NP_001372008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE10A	ENST00000539869.4	c.2784-11655G>A		intron_variant	Intron 18 of 21	1	NM_001385079.1	ENSP00000438284.3

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70659 AN: 151760 Hom.: 17272 Cov.: 32

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.466 AC: 70755 AN: 151878 Hom.: 17314 Cov.: 32 AF XY: 0.467 AC XY: 34666 AN XY: 74214

African (AFR) AF: 0.629 AC: 26050 AN: 41418

American (AMR) AF: 0.470 AC: 7167 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1265 AN: 3472

East Asian (EAS) AF: 0.425 AC: 2187 AN: 5146

South Asian (SAS) AF: 0.374 AC: 1803 AN: 4824

European-Finnish (FIN) AF: 0.426 AC: 4486 AN: 10526

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26407 AN: 67928

Other (OTH) AF: 0.440 AC: 927 AN: 2106

Alfa AF: 0.453 Hom.: 2108

Bravo AF: 0.472

Asia WGS AF: 0.457 AC: 1589 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.7
DANN	Benign	0.60
PhyloP100		0.12

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: rs512584; hg19: chr6-165768646;