rs220771

Positions:

• chr6-165407913-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000539869.4(PDE10A):​c.2076+5588G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,110 control chromosomes in the GnomAD database, including 3,231 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 0.20 (3231 hom., cov: 33)
• Consequence: PDE10A ENST00000539869.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE10A	NM_001385079.1	c.2076+5588G>A		intron_variant		ENST00000539869.4	NP_001372008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE10A	ENST00000539869.4	c.2076+5588G>A		intron_variant		1	NM_001385079.1	ENSP00000438284	P3

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30657 AN: 151992 Hom.: 3230 Cov.: 33

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.0890

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.202 AC: 30681 AN: 152110 Hom.: 3231 Cov.: 33 AF XY: 0.198 AC XY: 14728 AN XY: 74370

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.0896

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.229

Alfa AF: 0.214 Hom.: 4944

Bravo AF: 0.207

Asia WGS AF: 0.164 AC: 570 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.83
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs220771; hg19: chr6-165821402;