rs4644166

Variant names:

• chr7-83150474-A-G
• rs4644166
• NM_033026.6:c.1893+4274T>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.1893+4274T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0587 in 152,286 control chromosomes in the GnomAD database, including 579 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 0.059 (579 hom., cov: 32)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.380
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCLO	NM_033026.6	c.1893+4274T>C		intron_variant	Intron 2 of 24	ENST00000333891.14	NP_149015.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCLO	ENST00000333891.14	c.1893+4274T>C		intron_variant	Intron 2 of 24	2	NM_033026.6	ENSP00000334319.8
PCLO	ENST00000423517.6	c.1893+4274T>C		intron_variant	Intron 2 of 19	5		ENSP00000388393.2

Frequencies

GnomAD3 genomes AF: 0.0587 AC: 8928 AN: 152168 Hom.: 576 Cov.: 32

Gnomad AFR AF: 0.0149

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.0913

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.0120

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0490

Gnomad OTH AF: 0.0722

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

GnomAD4 genome AF: 0.0587 AC: 8940 AN: 152286 Hom.: 579 Cov.: 32 AF XY: 0.0612 AC XY: 4557 AN XY: 74454

African (AFR) AF: 0.0148 AC: 617 AN: 41574

American (AMR) AF: 0.154 AC: 2360 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0913 AC: 317 AN: 3472

East Asian (EAS) AF: 0.260 AC: 1337 AN: 5150

South Asian (SAS) AF: 0.139 AC: 671 AN: 4824

European-Finnish (FIN) AF: 0.0120 AC: 128 AN: 10624

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0490 AC: 3331 AN: 68028

Other (OTH) AF: 0.0710 AC: 150 AN: 2112

Alfa AF: 0.0647 Hom.: 100

Bravo AF: 0.0689

Asia WGS AF: 0.169 AC: 588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.5
DANN	Benign	0.57
PhyloP100		0.38
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: rs4644166; hg19: chr7-82779790;