rs7762160

Variant names:

• chr6-165601943-T-C
• rs7762160
• NM_001385079.1:c.866-58375A>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.866-58375A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 152,038 control chromosomes in the GnomAD database, including 10,383 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 0.36 (10383 hom., cov: 32)
• Consequence: PDE10A NM_001385079.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE10A	NM_001385079.1	c.866-58375A>G		intron_variant	Intron 1 of 21	ENST00000539869.4	NP_001372008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE10A	ENST00000539869.4	c.866-58375A>G		intron_variant	Intron 1 of 21	1	NM_001385079.1	ENSP00000438284.3

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55336 AN: 151920 Hom.: 10371 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.364 AC: 55373 AN: 152038 Hom.: 10383 Cov.: 32 AF XY: 0.364 AC XY: 27056 AN XY: 74286

African (AFR) AF: 0.282 AC: 11681 AN: 41482

American (AMR) AF: 0.333 AC: 5089 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1510 AN: 3468

East Asian (EAS) AF: 0.328 AC: 1697 AN: 5168

South Asian (SAS) AF: 0.504 AC: 2426 AN: 4810

European-Finnish (FIN) AF: 0.379 AC: 3995 AN: 10548

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.406 AC: 27625 AN: 67976

Other (OTH) AF: 0.410 AC: 866 AN: 2110

Alfa AF: 0.397 Hom.: 53183

Bravo AF: 0.354

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.26
PhyloP100		-0.10

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: rs7762160; hg19: chr6-166015431; COSMIC: COSV64840446;