6-165755520-G-T

Position:

• chr6-165755520-G-T

Variant summary

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

The ENST00000435810.1(ENSG00000236627):​n.194+1138G>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 0.174 in 152,018 control chromosomes in the GnomAD database, including 2,661 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 0.17 (2661 hom., cov: 32)
• Consequence: ENST00000435810.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE10A	XM_011535387.4	c.59-44367C>A		intron_variant			XP_011533689.2
PDE10A	XM_017010194.3	c.59-44367C>A		intron_variant			XP_016865683.1
PDE10A	XM_017010197.3	c.59-44367C>A		intron_variant			XP_016865686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000435810.1	n.194+1138G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26486 AN: 151900 Hom.: 2651 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.0640

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.174 AC: 26519 AN: 152018 Hom.: 2661 Cov.: 32 AF XY: 0.179 AC XY: 13333 AN XY: 74322

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.0640

Gnomad4 EAS AF: 0.363

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.138

Alfa AF: 0.105 Hom.: 229

Bravo AF: 0.174

Asia WGS AF: 0.238 AC: 827 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.77
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1546141; hg19: chr6-166169008;