rs7781142

Variant names:

• chr7-82933795-A-G
• rs7781142
• NM_033026.6:c.11112+15681T>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.11112+15681T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 151,794 control chromosomes in the GnomAD database, including 23,410 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 0.55 (23410 hom., cov: 32)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.313
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCLO	NM_033026.6	c.11112+15681T>C		intron_variant	Intron 6 of 24	ENST00000333891.14	NP_149015.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCLO	ENST00000333891.14	c.11112+15681T>C		intron_variant	Intron 6 of 24	2	NM_033026.6	ENSP00000334319.8
PCLO	ENST00000437081.1	c.1272+15681T>C		intron_variant	Intron 1 of 1	1		ENSP00000393760.1
PCLO	ENST00000423517.6	c.11112+15681T>C		intron_variant	Intron 6 of 19	5		ENSP00000388393.2

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83386 AN: 151676 Hom.: 23369 Cov.: 32

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.550 AC: 83482 AN: 151794 Hom.: 23410 Cov.: 32 AF XY: 0.551 AC XY: 40899 AN XY: 74214

African (AFR) AF: 0.564 AC: 23409 AN: 41478

American (AMR) AF: 0.576 AC: 8751 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1648 AN: 3464

East Asian (EAS) AF: 0.802 AC: 4131 AN: 5150

South Asian (SAS) AF: 0.603 AC: 2909 AN: 4826

European-Finnish (FIN) AF: 0.514 AC: 5442 AN: 10578

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35480 AN: 67798

Other (OTH) AF: 0.551 AC: 1161 AN: 2108

Alfa AF: 0.527 Hom.: 26933

Bravo AF: 0.556

Asia WGS AF: 0.703 AC: 2440 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.4
DANN	Benign	0.41
PhyloP100		-0.31
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: rs7781142; hg19: chr7-82563111;