NM_033026.6:c.13655-6112A>G

Variant names:

• chr7-82853359-T-C
• rs6972720
• NM_033026.6:c.13655-6112A>G

Variant summary

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

The NM_033026.6(PCLO):​c.13655-6112A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.836 in 151,880 control chromosomes in the GnomAD database, including 53,540 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 0.84 (53540 hom., cov: 30)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• 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 (AFR) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCLO	NM_033026.6	c.13655-6112A>G		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.13655-6112A>G		intron_variant	Intron 10 of 24	2	NM_033026.6	ENSP00000334319.8

Frequencies

GnomAD3 genomes AF: 0.836 AC: 126944 AN: 151762 Hom.: 53499 Cov.: 30

Gnomad AFR AF: 0.893

Gnomad AMI AF: 0.683

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.594

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.842

Gnomad OTH AF: 0.810

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

GnomAD4 genome AF: 0.836 AC: 127044 AN: 151880 Hom.: 53540 Cov.: 30 AF XY: 0.834 AC XY: 61865 AN XY: 74216

African (AFR) AF: 0.893 AC: 37029 AN: 41462

American (AMR) AF: 0.784 AC: 11941 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.849 AC: 2946 AN: 3468

East Asian (EAS) AF: 0.594 AC: 3026 AN: 5098

South Asian (SAS) AF: 0.666 AC: 3207 AN: 4812

European-Finnish (FIN) AF: 0.861 AC: 9106 AN: 10578

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.842 AC: 57204 AN: 67922

Other (OTH) AF: 0.807 AC: 1702 AN: 2108

Alfa AF: 0.850 Hom.: 14557

Bravo AF: 0.833

Asia WGS AF: 0.622 AC: 2165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.20
DANN	Benign	0.47
PhyloP100		-1.5
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: rs6972720; hg19: chr7-82482675;