chr7-82819089-C-T

Variant names:

• chr7-82819089-C-T
• rs2715147
• NM_033026.6:c.14791+3406G>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.14791+3406G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 151,908 control chromosomes in the GnomAD database, including 25,604 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 0.57 (25604 hom., cov: 32)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.978
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 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.14791+3406G>A		intron	N/A	NP_149015.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCLO	ENST00000333891.14	TSL:2 MANE Select	c.14791+3406G>A		intron	N/A	ENSP00000334319.8
	PCLO	ENST00000432078.2	TSL:5	n.279+2023G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86304 AN: 151790 Hom.: 25543 Cov.: 32

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.556

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

GnomAD4 genome AF: 0.569 AC: 86436 AN: 151908 Hom.: 25604 Cov.: 32 AF XY: 0.570 AC XY: 42307 AN XY: 74244

African (AFR) AF: 0.687 AC: 28473 AN: 41444

American (AMR) AF: 0.557 AC: 8495 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1583 AN: 3472

East Asian (EAS) AF: 0.850 AC: 4400 AN: 5176

South Asian (SAS) AF: 0.623 AC: 2997 AN: 4810

European-Finnish (FIN) AF: 0.493 AC: 5183 AN: 10516

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.493 AC: 33493 AN: 67930

Other (OTH) AF: 0.560 AC: 1182 AN: 2112

Alfa AF: 0.510 Hom.: 10133

Bravo AF: 0.579

Asia WGS AF: 0.737 AC: 2557 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.20
DANN	Benign	0.40
PhyloP100		-0.98
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: rs2715147; hg19: chr7-82448405;