chr7-82857151-C-G

Variant names:

• chr7-82857151-C-G
• rs12707523
• NM_033026.6:c.13655-9904G>C

Variant summary

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

The ENST00000333891.14(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 ENST00000333891.14 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505
• Publications: 3 publications found

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]

PCLO Gene-Disease associations (from GenCC):

• pontocerebellar hypoplasia type 3

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000333891.14. 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
	PCLO	NM_033026.6	MANE Select	c.13655-9904G>C		intron	N/A	NP_149015.2
	PCLO	NM_014510.3		c.13655-9904G>C		intron	N/A	NP_055325.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCLO	ENST00000333891.14	TSL:2 MANE Select	c.13655-9904G>C		intron	N/A	ENSP00000334319.8
	PCLO	ENST00000426442.6	TSL:1	n.185-9904G>C		intron	N/A
	PCLO	ENST00000423517.6	TSL:5	c.13655-9904G>C		intron	N/A	ENSP00000388393.2

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

African (AFR) AF: 0.191 AC: 7905 AN: 41462

American (AMR) AF: 0.222 AC: 3383 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 917 AN: 3468

East Asian (EAS) AF: 0.290 AC: 1489 AN: 5134

South Asian (SAS) AF: 0.260 AC: 1251 AN: 4814

European-Finnish (FIN) AF: 0.338 AC: 3566 AN: 10546

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19866 AN: 67966

Other (OTH) AF: 0.247 AC: 522 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.3
DANN	Benign	0.60
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12707523; hg19: chr7-82486467;