Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP7

The NM_033026.6(PCLO):c.7272C>T(p.Pro2424Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 20)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PCLO
NM_033026.6 synonymous

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.596

Publications

0 publications found

Variant links:

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

PCLO links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP7

Synonymous conserved (PhyloP=-0.596 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033026.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCLO	NM_033026.6	MANE Select	c.7272C>T	p.Pro2424Pro	synonymous	Exon 5 of 25	NP_149015.2
	PCLO	NM_014510.3		c.7272C>T	p.Pro2424Pro	synonymous	Exon 5 of 20	NP_055325.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCLO	ENST00000333891.14	TSL:2 MANE Select	c.7272C>T	p.Pro2424Pro	synonymous	Exon 5 of 25	ENSP00000334319.8
	PCLO	ENST00000423517.6	TSL:5	c.7272C>T	p.Pro2424Pro	synonymous	Exon 5 of 20	ENSP00000388393.2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

137180

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1154486

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

577474

African (AFR)

AF:

0.00

AC:

AN:

27010

American (AMR)

AF:

0.00

AC:

AN:

34496

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21976

East Asian (EAS)

AF:

0.00

AC:

AN:

34358

South Asian (SAS)

AF:

0.00

AC:

AN:

70426

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38266

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3754

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

874206

Other (OTH)

AF:

0.00

AC:

AN:

49994

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

137180

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

66066

African (AFR)

AF:

0.00

AC:

AN:

36856

American (AMR)

AF:

0.00

AC:

AN:

13470

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3282

East Asian (EAS)

AF:

0.00

AC:

AN:

4264

South Asian (SAS)

AF:

0.00

AC:

AN:

3910

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9008

Middle Eastern (MID)

AF:

0.00

AC:

AN:

274

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

63390

Other (OTH)

AF:

0.00

AC:

AN:

1854

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.69

(source)

DANN

Benign

0.51

PhyloP100

-0.60

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

7-82953681-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over