chr7-82766415-G-A

Variant names:

• chr7-82766415-G-A
• rs1157530
• NM_033026.6:c.15008-4922C>T

Variant summary

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

The NM_033026.6(PCLO):​c.15008-4922C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 151,692 control chromosomes in the GnomAD database, including 17,374 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 0.46 (17374 hom., cov: 31)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164
• Publications: 1 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 = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCLO	NM_033026.6	c.15008-4922C>T		intron_variant	Intron 22 of 24	ENST00000333891.14	NP_149015.2
PCLO	XM_047420210.1	c.15191-4922C>T		intron_variant	Intron 23 of 25		XP_047276166.1
PCLO	XM_047420211.1	c.14717-4922C>T		intron_variant	Intron 23 of 25		XP_047276167.1
PCLO	XM_017012006.3	c.8096-4922C>T		intron_variant	Intron 21 of 23		XP_016867495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCLO	ENST00000333891.14	c.15008-4922C>T		intron_variant	Intron 22 of 24	2	NM_033026.6	ENSP00000334319.8

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69469 AN: 151574 Hom.: 17355 Cov.: 31

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.458 AC: 69520 AN: 151692 Hom.: 17374 Cov.: 31 AF XY: 0.462 AC XY: 34261 AN XY: 74086

African (AFR) AF: 0.268 AC: 11092 AN: 41416

American (AMR) AF: 0.499 AC: 7573 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1672 AN: 3468

East Asian (EAS) AF: 0.724 AC: 3709 AN: 5124

South Asian (SAS) AF: 0.641 AC: 3081 AN: 4810

European-Finnish (FIN) AF: 0.506 AC: 5303 AN: 10490

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.522 AC: 35439 AN: 67880

Other (OTH) AF: 0.466 AC: 983 AN: 2108

Alfa AF: 0.492 Hom.: 6081

Bravo AF: 0.449

Asia WGS AF: 0.654 AC: 2272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.6
DANN	Benign	0.67
PhyloP100		0.16
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: rs1157530; hg19: chr7-82395731;