chr7-82765925-G-T

Variant names:

• chr7-82765925-G-T
• rs34608268
• NM_033026.6:c.15008-4432C>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.15008-4432C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 151,722 control chromosomes in the GnomAD database, including 18,808 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 0.48 (18808 hom., cov: 30)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288
• Publications: 2 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.705 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCLO	NM_033026.6	MANE Select	c.15008-4432C>A		intron	N/A	NP_149015.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCLO	ENST00000333891.14	TSL:2 MANE Select	c.15008-4432C>A		intron	N/A	ENSP00000334319.8

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73348 AN: 151604 Hom.: 18785 Cov.: 30

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.484 AC: 73424 AN: 151722 Hom.: 18808 Cov.: 30 AF XY: 0.487 AC XY: 36135 AN XY: 74152

African (AFR) AF: 0.332 AC: 13763 AN: 41412

American (AMR) AF: 0.519 AC: 7891 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1715 AN: 3468

East Asian (EAS) AF: 0.725 AC: 3732 AN: 5150

South Asian (SAS) AF: 0.640 AC: 3088 AN: 4824

European-Finnish (FIN) AF: 0.510 AC: 5361 AN: 10522

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.533 AC: 36170 AN: 67844

Other (OTH) AF: 0.487 AC: 1021 AN: 2098

Alfa AF: 0.504 Hom.: 3360

Bravo AF: 0.476

Asia WGS AF: 0.659 AC: 2287 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.3
DANN	Benign	0.66
PhyloP100		0.29
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: rs34608268; hg19: chr7-82395241;