chr7-82932008-T-C

Variant names:

• chr7-82932008-T-C
• rs9690648
• NM_033026.6:c.11113-15135A>G

Variant summary

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

The NM_033026.6(PCLO):​c.11113-15135A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,080 control chromosomes in the GnomAD database, including 5,810 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 (5810 hom., cov: 32)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199
• Publications: 9 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033026.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCLO	NM_033026.6	MANE Select	c.11113-15135A>G		intron	N/A	NP_149015.2	Q9Y6V0-5
	PCLO	NM_014510.3		c.11113-15135A>G		intron	N/A	NP_055325.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCLO	ENST00000333891.14	TSL:2 MANE Select	c.11113-15135A>G		intron	N/A	ENSP00000334319.8	Q9Y6V0-5
	PCLO	ENST00000437081.2	TSL:1	c.1273-15135A>G		intron	N/A	ENSP00000393760.2
	PCLO	ENST00000423517.6	TSL:5	c.11113-15135A>G		intron	N/A	ENSP00000388393.2	Q9Y6V0-6

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29957 AN: 151962 Hom.: 5787 Cov.: 32

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.0642

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0196

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0704

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.198 AC: 30041 AN: 152080 Hom.: 5810 Cov.: 32 AF XY: 0.193 AC XY: 14329 AN XY: 74342

African (AFR) AF: 0.498 AC: 20662 AN: 41464

American (AMR) AF: 0.163 AC: 2483 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.0642 AC: 223 AN: 3472

East Asian (EAS) AF: 0.121 AC: 626 AN: 5160

South Asian (SAS) AF: 0.110 AC: 533 AN: 4826

European-Finnish (FIN) AF: 0.0196 AC: 208 AN: 10620

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0704 AC: 4787 AN: 67980

Other (OTH) AF: 0.178 AC: 376 AN: 2108

Alfa AF: 0.113 Hom.: 3784

Bravo AF: 0.221

Asia WGS AF: 0.151 AC: 523 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.2
DANN	Benign	0.47
PhyloP100		0.20
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: rs9690648; hg19: chr7-82561324;