Genetic Variant PCLO:c.14791+1776T>A (chr7-82820719-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_033026.6(PCLO):c.14791+1776T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PCLO
NM_033026.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.430

Publications

26 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCLO	NM_033026.6 link	c.14791+1776T>A		intron_variant	Intron 20 of 24	ENST00000333891.14	NP_149015.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PCLO	ENST00000333891.14 link	c.14791+1776T>A	intron_variant	Intron 20 of 24	2	NM_033026.6	ENSP00000334319.8	Q9Y6V0-5
PCLO	ENST00000423517.6 link	c.*1759T>A	3_prime_UTR_variant	Exon 20 of 20	5		ENSP00000388393.2	Q9Y6V0-6
PCLO	ENST00000432078.2 link	n.279+393T>A	intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

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

AF:

0.00

AC:

AN:

1078960

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

509324

African (AFR)

AF:

0.00

AC:

AN:

22948

American (AMR)

AF:

0.00

AC:

AN:

8414

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14382

East Asian (EAS)

AF:

0.00

AC:

AN:

26480

South Asian (SAS)

AF:

0.00

AC:

AN:

19484

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21094

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2912

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

919602

Other (OTH)

AF:

0.00

AC:

AN:

43644

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

0.43

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over