chr6-165717956-C-T

Variant names:

• chr6-165717956-C-T
• rs6919646
• ENST00000647768.3:c.107-6803G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000647768.3(PDE10A):​c.107-6803G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 152,074 control chromosomes in the GnomAD database, including 32,683 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 0.65 (32683 hom., cov: 32)
• Consequence: PDE10A ENST00000647768.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.646
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000647768.3. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE10A	ENST00000647768.3		c.107-6803G>A		intron	N/A	ENSP00000497930.3
	PDE10A	ENST00000672902.1		c.-17-6803G>A		intron	N/A	ENSP00000500351.1
	PDE10A	ENST00000672859.1		c.-17-6803G>A		intron	N/A	ENSP00000500900.1

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98449 AN: 151956 Hom.: 32652 Cov.: 32

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.672

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.619

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

GnomAD4 genome AF: 0.648 AC: 98520 AN: 152074 Hom.: 32683 Cov.: 32 AF XY: 0.642 AC XY: 47718 AN XY: 74314

African (AFR) AF: 0.784 AC: 32541 AN: 41500

American (AMR) AF: 0.521 AC: 7960 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.672 AC: 2332 AN: 3472

East Asian (EAS) AF: 0.634 AC: 3274 AN: 5166

South Asian (SAS) AF: 0.714 AC: 3441 AN: 4818

European-Finnish (FIN) AF: 0.513 AC: 5415 AN: 10554

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.608 AC: 41352 AN: 67982

Other (OTH) AF: 0.617 AC: 1302 AN: 2110

Alfa AF: 0.624 Hom.: 3547

Bravo AF: 0.650

Asia WGS AF: 0.685 AC: 2385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.58
PhyloP100		-0.65

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6919646; hg19: chr6-166131444;