6-165627133-A-T

Variant names:

• chr6-165627133-A-T
• rs4709082
• NM_001385079.1:c.865+34814T>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.865+34814T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 152,054 control chromosomes in the GnomAD database, including 23,543 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 0.54 (23543 hom., cov: 32)
• Consequence: PDE10A NM_001385079.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• dyskinesia, limb and orofacial, infantile-onset

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Genomics England PanelApp
• 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=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.708 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE10A	NM_001385079.1	MANE Select	c.865+34814T>A		intron	N/A	NP_001372008.1	Q9Y233-3
	PDE10A	NM_001130690.3		c.67+34814T>A		intron	N/A	NP_001124162.1	Q9Y233-2
	PDE10A	NM_006661.4		c.-92+34814T>A		intron	N/A	NP_006652.1	A0A1B1UZR0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE10A	ENST00000539869.4	TSL:1 MANE Select	c.865+34814T>A		intron	N/A	ENSP00000438284.3	Q9Y233-3
	PDE10A	ENST00000647768.3		c.242-83565T>A		intron	N/A	ENSP00000497930.3	A0A3B3ITT8
	PDE10A	ENST00000672902.1		c.119-83565T>A		intron	N/A	ENSP00000500351.1	A0A5F9ZHF9

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81638 AN: 151938 Hom.: 23518 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.537 AC: 81700 AN: 152054 Hom.: 23543 Cov.: 32 AF XY: 0.542 AC XY: 40244 AN XY: 74310

African (AFR) AF: 0.325 AC: 13470 AN: 41454

American (AMR) AF: 0.651 AC: 9958 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1990 AN: 3470

East Asian (EAS) AF: 0.727 AC: 3762 AN: 5174

South Asian (SAS) AF: 0.443 AC: 2135 AN: 4814

European-Finnish (FIN) AF: 0.655 AC: 6919 AN: 10566

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.615 AC: 41794 AN: 67966

Other (OTH) AF: 0.533 AC: 1125 AN: 2110

Alfa AF: 0.583 Hom.: 3359

Bravo AF: 0.533

Asia WGS AF: 0.538 AC: 1869 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	0.081
DANN	Benign	0.45
PhyloP100		-1.3

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: rs4709082; hg19: chr6-166040621;