7-82874093-C-T

Variant names:

• chr7-82874093-C-T
• rs2888019
• NM_033026.6:c.13654+5244G>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.13654+5244G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 151,796 control chromosomes in the GnomAD database, including 14,518 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 0.42 (14518 hom., cov: 32)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.499 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.13654+5244G>A		intron	N/A	NP_149015.2	Q9Y6V0-5
	PCLO	NM_014510.3		c.13654+5244G>A		intron	N/A	NP_055325.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCLO	ENST00000333891.14	TSL:2 MANE Select	c.13654+5244G>A		intron	N/A	ENSP00000334319.8	Q9Y6V0-5
	PCLO	ENST00000426442.6	TSL:1	n.184+5244G>A		intron	N/A
	PCLO	ENST00000423517.6	TSL:5	c.13654+5244G>A		intron	N/A	ENSP00000388393.2	Q9Y6V0-6

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63578 AN: 151680 Hom.: 14528 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.419 AC: 63564 AN: 151796 Hom.: 14518 Cov.: 32 AF XY: 0.419 AC XY: 31056 AN XY: 74158

African (AFR) AF: 0.277 AC: 11478 AN: 41384

American (AMR) AF: 0.432 AC: 6585 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1902 AN: 3460

East Asian (EAS) AF: 0.152 AC: 783 AN: 5166

South Asian (SAS) AF: 0.375 AC: 1800 AN: 4802

European-Finnish (FIN) AF: 0.507 AC: 5329 AN: 10512

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34198 AN: 67924

Other (OTH) AF: 0.433 AC: 912 AN: 2108

Alfa AF: 0.463 Hom.: 8892

Bravo AF: 0.406

Asia WGS AF: 0.261 AC: 910 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.6
DANN	Benign	0.74
PhyloP100		-0.20
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: rs2888019; hg19: chr7-82503409;