rs10954694

Variant names:

• chr7-82927845-T-C
• rs10954694
• NM_033026.6:c.11113-10972A>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.11113-10972A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 151,996 control chromosomes in the GnomAD database, including 9,226 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 0.34 (9226 hom., cov: 32)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCLO	NM_033026.6	c.11113-10972A>G		intron_variant	Intron 6 of 24	ENST00000333891.14	NP_149015.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCLO	ENST00000333891.14	c.11113-10972A>G		intron_variant	Intron 6 of 24	2	NM_033026.6	ENSP00000334319.8
PCLO	ENST00000437081.1	c.1273-10972A>G		intron_variant	Intron 1 of 1	1		ENSP00000393760.1
PCLO	ENST00000423517.6	c.11113-10972A>G		intron_variant	Intron 6 of 19	5		ENSP00000388393.2

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51208 AN: 151878 Hom.: 9220 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.337 AC: 51243 AN: 151996 Hom.: 9226 Cov.: 32 AF XY: 0.342 AC XY: 25426 AN XY: 74268

African (AFR) AF: 0.221 AC: 9156 AN: 41486

American (AMR) AF: 0.397 AC: 6056 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1289 AN: 3468

East Asian (EAS) AF: 0.486 AC: 2515 AN: 5170

South Asian (SAS) AF: 0.409 AC: 1968 AN: 4816

European-Finnish (FIN) AF: 0.404 AC: 4256 AN: 10526

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24865 AN: 67952

Other (OTH) AF: 0.351 AC: 740 AN: 2106

Alfa AF: 0.357 Hom.: 36864

Bravo AF: 0.335

Asia WGS AF: 0.463 AC: 1608 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.1
DANN	Benign	0.76
PhyloP100		0.051
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: rs10954694; hg19: chr7-82557161;