6-165471299-T-C

Variant names:

• chr6-165471299-T-C
• rs475061
• NM_001385079.1:c.1023+11016A>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.1023+11016A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 151,960 control chromosomes in the GnomAD database, including 21,694 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 0.53 (21694 hom., cov: 31)
• Consequence: PDE10A NM_001385079.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31
• Publications: 2 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 (EAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE10A	NM_001385079.1	c.1023+11016A>G		intron_variant	Intron 3 of 21	ENST00000539869.4	NP_001372008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE10A	ENST00000539869.4	c.1023+11016A>G		intron_variant	Intron 3 of 21	1	NM_001385079.1	ENSP00000438284.3

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80824 AN: 151842 Hom.: 21676 Cov.: 31

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.532 AC: 80877 AN: 151960 Hom.: 21694 Cov.: 31 AF XY: 0.537 AC XY: 39901 AN XY: 74276

African (AFR) AF: 0.571 AC: 23647 AN: 41422

American (AMR) AF: 0.528 AC: 8056 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1737 AN: 3468

East Asian (EAS) AF: 0.571 AC: 2946 AN: 5160

South Asian (SAS) AF: 0.500 AC: 2407 AN: 4814

European-Finnish (FIN) AF: 0.637 AC: 6720 AN: 10544

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33576 AN: 67970

Other (OTH) AF: 0.507 AC: 1069 AN: 2110

Alfa AF: 0.495 Hom.: 16261

Bravo AF: 0.529

Asia WGS AF: 0.522 AC: 1815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.090
DANN	Benign	0.58
PhyloP100		-2.3

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: rs475061; hg19: chr6-165884787; COSMIC: COSV63093616;