rs12707523

chr7-82857151-C-G

Variant summary

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

The NM_033026.6(PCLO):c.13655-9904G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 151,952 control chromosomes in the GnomAD database, including 5,366 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 0.26 (5366 hom., cov: 32)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505

Genes affected

PCLO (HGNC:13406): (piccolo presynaptic cytomatrix protein) The protein encoded by this gene is part of the presynaptic cytoskeletal matrix, which is involved in establishing active synaptic zones and in synaptic vesicle trafficking. Variations in this gene have been associated with bipolar disorder and major depressive disorder. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCLO	NM_033026.6	c.13655-9904G>C		intron_variant		ENST00000333891.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCLO	ENST00000333891.14	c.13655-9904G>C		intron_variant		2	NM_033026.6	P1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39092 AN: 151834 Hom.: 5356 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.258 AC: 39130 AN: 151952 Hom.: 5366 Cov.: 32 AF XY: 0.260 AC XY: 19290 AN XY: 74270

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.247

Alfa AF: 0.271 Hom.: 728

Bravo AF: 0.244

Asia WGS AF: 0.255 AC: 886 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	1.3
Dann	Benign	0.60

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: rs12707523; hg19: chr7-82486467;