rs13233504

Variant names:

• chr7-82868515-C-T
• rs13233504
• NM_033026.6:c.13654+10822G>A

Variant summary

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

The NM_033026.6(PCLO):​c.13654+10822G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,138 control chromosomes in the GnomAD database, including 2,600 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 (2600 hom., cov: 32)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.949
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCLO	NM_033026.6	c.13654+10822G>A		intron_variant	Intron 10 of 24	ENST00000333891.14	NP_149015.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCLO	ENST00000333891.14	c.13654+10822G>A		intron_variant	Intron 10 of 24	2	NM_033026.6	ENSP00000334319.8

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25972 AN: 152018 Hom.: 2597 Cov.: 32

Gnomad AFR AF: 0.0874

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.171 AC: 25993 AN: 152138 Hom.: 2600 Cov.: 32 AF XY: 0.174 AC XY: 12914 AN XY: 74348

African (AFR) AF: 0.0874 AC: 3631 AN: 41540

American (AMR) AF: 0.171 AC: 2606 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 759 AN: 3468

East Asian (EAS) AF: 0.135 AC: 697 AN: 5178

South Asian (SAS) AF: 0.174 AC: 838 AN: 4820

European-Finnish (FIN) AF: 0.247 AC: 2611 AN: 10574

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14344 AN: 67990

Other (OTH) AF: 0.163 AC: 343 AN: 2100

Alfa AF: 0.193 Hom.: 1712

Bravo AF: 0.160

Asia WGS AF: 0.131 AC: 456 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.0
DANN	Benign	0.69
PhyloP100		-0.95
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: rs13233504; hg19: chr7-82497831;