7-82934200-C-G

Variant names:

• chr7-82934200-C-G
• rs7799260
• NM_033026.6:c.11112+15276G>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+15276G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 151,604 control chromosomes in the GnomAD database, including 28,053 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 0.60 (28053 hom., cov: 31)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCLO	NM_033026.6	c.11112+15276G>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+15276G>C		intron_variant	Intron 6 of 24	2	NM_033026.6	ENSP00000334319.8
PCLO	ENST00000437081.1	c.1272+15276G>C		intron_variant	Intron 1 of 1	1		ENSP00000393760.1
PCLO	ENST00000423517.6	c.11112+15276G>C		intron_variant	Intron 6 of 19	5		ENSP00000388393.2

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90512 AN: 151492 Hom.: 28003 Cov.: 31

Gnomad AFR AF: 0.730

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.803

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.583

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

GnomAD4 genome AF: 0.598 AC: 90622 AN: 151604 Hom.: 28053 Cov.: 31 AF XY: 0.597 AC XY: 44226 AN XY: 74084

African (AFR) AF: 0.730 AC: 30226 AN: 41418

American (AMR) AF: 0.594 AC: 9013 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1653 AN: 3460

East Asian (EAS) AF: 0.804 AC: 4146 AN: 5158

South Asian (SAS) AF: 0.612 AC: 2943 AN: 4806

European-Finnish (FIN) AF: 0.513 AC: 5407 AN: 10540

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35445 AN: 67724

Other (OTH) AF: 0.585 AC: 1233 AN: 2106

Alfa AF: 0.556 Hom.: 3040

Bravo AF: 0.611

Asia WGS AF: 0.727 AC: 2522 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.87
DANN	Benign	0.20
PhyloP100		0.22
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: rs7799260; hg19: chr7-82563516;