7-82987519-C-G

Variant names:

• chr7-82987519-C-G
• rs7778238
• NM_033026.6:c.3301-21032G>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.3301-21032G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 151,738 control chromosomes in the GnomAD database, including 19,531 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 0.50 (19531 hom., cov: 31)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.767
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.777 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.3301-21032G>C		intron	N/A	NP_149015.2
	PCLO	NM_014510.3		c.3301-21032G>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.3301-21032G>C		intron	N/A	ENSP00000334319.8
	PCLO	ENST00000423517.6	TSL:5	c.3301-21032G>C		intron	N/A	ENSP00000388393.2
	PCLO	ENST00000461143.1	TSL:2	n.362-21032G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.501 AC: 75896 AN: 151620 Hom.: 19500 Cov.: 31

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.797

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.522

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

GnomAD4 genome AF: 0.501 AC: 75965 AN: 151738 Hom.: 19531 Cov.: 31 AF XY: 0.503 AC XY: 37274 AN XY: 74134

African (AFR) AF: 0.458 AC: 18958 AN: 41392

American (AMR) AF: 0.549 AC: 8353 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1623 AN: 3466

East Asian (EAS) AF: 0.798 AC: 4120 AN: 5164

South Asian (SAS) AF: 0.564 AC: 2721 AN: 4822

European-Finnish (FIN) AF: 0.466 AC: 4908 AN: 10522

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33656 AN: 67842

Other (OTH) AF: 0.526 AC: 1106 AN: 2104

Alfa AF: 0.491 Hom.: 2302

Bravo AF: 0.507

Asia WGS AF: 0.678 AC: 2347 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.25
DANN	Benign	0.36
PhyloP100		-0.77
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: rs7778238; hg19: chr7-82616835;