7-82874126-T-C

Variant names:

• chr7-82874126-T-C
• rs1986742
• NM_033026.6:c.13654+5211A>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.13654+5211A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,968 control chromosomes in the GnomAD database, including 14,531 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 0.42 (14531 hom., cov: 32)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCLO	NM_033026.6	c.13654+5211A>G		intron_variant	Intron 10 of 24	ENST00000333891.14	NP_149015.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCLO	ENST00000333891.14	c.13654+5211A>G		intron_variant	Intron 10 of 24	2	NM_033026.6	ENSP00000334319.8

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63594 AN: 151850 Hom.: 14541 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.418 AC: 63581 AN: 151968 Hom.: 14531 Cov.: 32 AF XY: 0.418 AC XY: 31058 AN XY: 74236

African (AFR) AF: 0.277 AC: 11477 AN: 41472

American (AMR) AF: 0.432 AC: 6590 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1904 AN: 3466

East Asian (EAS) AF: 0.151 AC: 782 AN: 5176

South Asian (SAS) AF: 0.376 AC: 1811 AN: 4822

European-Finnish (FIN) AF: 0.506 AC: 5311 AN: 10506

Middle Eastern (MID) AF: 0.510 AC: 149 AN: 292

European-Non Finnish (NFE) AF: 0.503 AC: 34217 AN: 67970

Other (OTH) AF: 0.433 AC: 912 AN: 2106

Alfa AF: 0.435 Hom.: 2790

Bravo AF: 0.406

Asia WGS AF: 0.261 AC: 909 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.9
DANN	Benign	0.39
PhyloP100		0.24
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: rs1986742; hg19: chr7-82503442;