7-82849099-T-G

Variant names:

• chr7-82849099-T-G
• rs2522840
• NM_033026.6:c.13655-1852A>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_033026.6(PCLO):​c.13655-1852A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 151,932 control chromosomes in the GnomAD database, including 12,621 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 0.39 (12621 hom., cov: 32)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.490
• Publications: 10 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 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.13655-1852A>C		intron	N/A	NP_149015.2
	PCLO	NM_014510.3		c.13655-1852A>C		intron	N/A	NP_055325.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCLO	ENST00000333891.14	TSL:2 MANE Select	c.13655-1852A>C		intron	N/A	ENSP00000334319.8
	PCLO	ENST00000426442.6	TSL:1	n.185-1852A>C		intron	N/A
	PCLO	ENST00000423517.6	TSL:5	c.13655-1852A>C		intron	N/A	ENSP00000388393.2

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58962 AN: 151814 Hom.: 12605 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.388 AC: 59010 AN: 151932 Hom.: 12621 Cov.: 32 AF XY: 0.396 AC XY: 29385 AN XY: 74248

African (AFR) AF: 0.228 AC: 9451 AN: 41482

American (AMR) AF: 0.419 AC: 6386 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1379 AN: 3472

East Asian (EAS) AF: 0.698 AC: 3590 AN: 5144

South Asian (SAS) AF: 0.572 AC: 2756 AN: 4818

European-Finnish (FIN) AF: 0.472 AC: 4966 AN: 10522

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29139 AN: 67932

Other (OTH) AF: 0.398 AC: 840 AN: 2112

Alfa AF: 0.398 Hom.: 2636

Bravo AF: 0.376

Asia WGS AF: 0.621 AC: 2149 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Benign	0.83
PhyloP100		0.49
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: rs2522840; hg19: chr7-82478415;