chr6-165633546-A-G

Variant names:

• chr6-165633546-A-G
• rs1079418
• NM_001385079.1:c.865+28401T>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.865+28401T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 152,094 control chromosomes in the GnomAD database, including 7,875 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 0.32 (7875 hom., cov: 33)
• Consequence: PDE10A NM_001385079.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.135
• Publications: 6 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 (AFR) allele frequency at 95% confidence interval = 0.37 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+28401T>C		intron	N/A	NP_001372008.1
	PDE10A	NM_001130690.3		c.67+28401T>C		intron	N/A	NP_001124162.1
	PDE10A	NM_006661.4		c.-92+28401T>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.865+28401T>C		intron	N/A	ENSP00000438284.3
	PDE10A	ENST00000647768.3		c.241+77473T>C		intron	N/A	ENSP00000497930.3
	PDE10A	ENST00000672902.1		c.118+77473T>C		intron	N/A	ENSP00000500351.1

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48252 AN: 151976 Hom.: 7865 Cov.: 33

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.317 AC: 48283 AN: 152094 Hom.: 7875 Cov.: 33 AF XY: 0.316 AC XY: 23485 AN XY: 74348

African (AFR) AF: 0.375 AC: 15520 AN: 41434

American (AMR) AF: 0.247 AC: 3779 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1291 AN: 3472

East Asian (EAS) AF: 0.160 AC: 827 AN: 5176

South Asian (SAS) AF: 0.362 AC: 1747 AN: 4826

European-Finnish (FIN) AF: 0.260 AC: 2751 AN: 10584

Middle Eastern (MID) AF: 0.497 AC: 145 AN: 292

European-Non Finnish (NFE) AF: 0.310 AC: 21106 AN: 68002

Other (OTH) AF: 0.333 AC: 704 AN: 2114

Alfa AF: 0.311 Hom.: 985

Bravo AF: 0.318

Asia WGS AF: 0.277 AC: 960 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.30
PhyloP100		0.14

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: rs1079418; hg19: chr6-166047034;