rs12707524

Variant names:

• chr7-82857299-A-G
• rs12707524
• NM_033026.6:c.13655-10052T>C

Variant summary

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

The NM_033026.6(PCLO):​c.13655-10052T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,066 control chromosomes in the GnomAD database, including 2,736 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 0.18 (2736 hom., cov: 32)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.856
• 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=-0.89).
• 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.13655-10052T>C		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.13655-10052T>C		intron_variant	Intron 10 of 24	2	NM_033026.6	ENSP00000334319.8

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27289 AN: 151948 Hom.: 2734 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.180 AC: 27315 AN: 152066 Hom.: 2736 Cov.: 32 AF XY: 0.182 AC XY: 13538 AN XY: 74326

African (AFR) AF: 0.115 AC: 4785 AN: 41524

American (AMR) AF: 0.180 AC: 2741 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 762 AN: 3472

East Asian (EAS) AF: 0.137 AC: 705 AN: 5164

South Asian (SAS) AF: 0.174 AC: 840 AN: 4820

European-Finnish (FIN) AF: 0.246 AC: 2602 AN: 10576

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.211 AC: 14347 AN: 67930

Other (OTH) AF: 0.175 AC: 370 AN: 2114

Alfa AF: 0.199 Hom.: 4799

Bravo AF: 0.171

Asia WGS AF: 0.142 AC: 495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.8
DANN	Benign	0.72
PhyloP100		0.86
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: rs12707524; hg19: chr7-82486615;