chr7-83070785-T-C

Variant names:

• chr7-83070785-T-C
• rs10487656
• NM_033026.6:c.3300+63465A>G

Variant summary

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

The NM_033026.6(PCLO):​c.3300+63465A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,052 control chromosomes in the GnomAD database, including 4,811 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 0.24 (4811 hom., cov: 32)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCLO	NM_033026.6	c.3300+63465A>G		intron_variant	Intron 3 of 24	ENST00000333891.14	NP_149015.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCLO	ENST00000333891.14	c.3300+63465A>G		intron_variant	Intron 3 of 24	2	NM_033026.6	ENSP00000334319.8
PCLO	ENST00000423517.6	c.3300+63465A>G		intron_variant	Intron 3 of 19	5		ENSP00000388393.2
PCLO	ENST00000461143.1	n.361+63465A>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35788 AN: 151936 Hom.: 4801 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.236 AC: 35844 AN: 152052 Hom.: 4811 Cov.: 32 AF XY: 0.240 AC XY: 17856 AN XY: 74352

African (AFR) AF: 0.289 AC: 11994 AN: 41486

American (AMR) AF: 0.295 AC: 4507 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 531 AN: 3468

East Asian (EAS) AF: 0.550 AC: 2830 AN: 5146

South Asian (SAS) AF: 0.275 AC: 1325 AN: 4822

European-Finnish (FIN) AF: 0.205 AC: 2165 AN: 10570

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11778 AN: 67978

Other (OTH) AF: 0.235 AC: 495 AN: 2110

Alfa AF: 0.202 Hom.: 475

Bravo AF: 0.248

Asia WGS AF: 0.423 AC: 1466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.19
DANN	Benign	0.89
PhyloP100		0.033
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: rs10487656; hg19: chr7-82700101;