6-165770715-C-T

Position:

• chr6-165770715-C-T

Variant summary

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

The ENST00000435810.1(ENSG00000236627):​n.195-4138C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,170 control chromosomes in the GnomAD database, including 2,604 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 0.16 (2604 hom., cov: 32)
• Consequence: ENST00000435810.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.983

Genes affected

(HGNC:):

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE10A	XM_011535387.4	c.59-59562G>A		intron_variant			XP_011533689.2
PDE10A	XM_017010194.3	c.59-59562G>A		intron_variant			XP_016865683.1
PDE10A	XM_017010197.3	c.59-59562G>A		intron_variant			XP_016865686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000435810.1	n.195-4138C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24488 AN: 152052 Hom.: 2600 Cov.: 32

Gnomad AFR AF: 0.0665

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.161 AC: 24496 AN: 152170 Hom.: 2604 Cov.: 32 AF XY: 0.170 AC XY: 12664 AN XY: 74378

Gnomad4 AFR AF: 0.0665

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.155

Alfa AF: 0.162 Hom.: 4558

Bravo AF: 0.149

Asia WGS AF: 0.357 AC: 1239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.79
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4709090; hg19: chr6-166184203;