Variant rs976714 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_033026.6(PCLO):c.8410G>A(p.Ala2804Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 1,613,526 control chromosomes in the GnomAD database, including 107,846 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.31 ( 8222 hom., cov: 32)

Exomes 𝑓: 0.37 ( 99624 hom. )

Consequence

PCLO
NM_033026.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.447

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.7973565E-5).

BP6

Variant 7-82952543-C-T is Benign according to our data. Variant chr7-82952543-C-T is described in ClinVar as [Benign]. Clinvar id is 1599232.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCLO	NM_033026.6 linkuse as main transcript	c.8410G>A	p.Ala2804Thr	missense_variant	5/25	ENST00000333891.14	NP_149015.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCLO	ENST00000333891.14 linkuse as main transcript	c.8410G>A	p.Ala2804Thr	missense_variant	5/25	2	NM_033026.6	ENSP00000334319.8		Q9Y6V0-5
PCLO	ENST00000423517.6 linkuse as main transcript	c.8410G>A	p.Ala2804Thr	missense_variant	5/20	5		ENSP00000388393.2		Q9Y6V0-6

Frequencies

GnomAD3 genomes

AF:

0.307

AC:

46608

AN:

151866

Hom.:

8213

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.326

Gnomad AMR

AF:

0.372

Gnomad ASJ

AF:

0.367

Gnomad EAS

AF:

0.472

Gnomad SAS

AF:

0.388

Gnomad FIN

AF:

0.397

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.363

Gnomad OTH

AF:

0.325

GnomAD3 exomes

AF:

0.370

AC:

92003

AN:

248980

Hom.:

17721

AF XY:

0.372

AC XY:

50252

AN XY:

135054

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.412

Gnomad ASJ exome

AF:

0.373

Gnomad EAS exome

AF:

0.496

Gnomad SAS exome

AF:

0.391

Gnomad FIN exome

AF:

0.390

Gnomad NFE exome

AF:

0.359

Gnomad OTH exome

AF:

0.376

GnomAD4 exome

AF:

0.366

AC:

535178

AN:

1461544

Hom.:

99624

Cov.:

AF XY:

0.367

AC XY:

267015

AN XY:

727066

show subpopulations

Gnomad4 AFR exome

AF:

0.123

Gnomad4 AMR exome

AF:

0.406

Gnomad4 ASJ exome

AF:

0.365

Gnomad4 EAS exome

AF:

0.476

Gnomad4 SAS exome

AF:

0.390

Gnomad4 FIN exome

AF:

0.391

Gnomad4 NFE exome

AF:

0.366

Gnomad4 OTH exome

AF:

0.358

GnomAD4 genome

AF:

0.307

AC:

46629

AN:

151982

Hom.:

8222

Cov.:

AF XY:

0.313

AC XY:

23223

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.131

Gnomad4 AMR

AF:

0.373

Gnomad4 ASJ

AF:

0.367

Gnomad4 EAS

AF:

0.473

Gnomad4 SAS

AF:

0.389

Gnomad4 FIN

AF:

0.397

Gnomad4 NFE

AF:

0.363

Gnomad4 OTH

AF:

0.327

Alfa

AF:

0.355

Hom.:

24456

Bravo

AF:

0.300

TwinsUK

AF:

0.367

AC:

1359

ALSPAC

AF:

0.355

AC:

1368

ESP6500AA

AF:

0.138

AC:

565

ESP6500EA

AF:

0.360

AC:

3018

ExAC

AF:

0.361

AC:

43639

EpiCase

AF:

0.358

EpiControl

AF:

0.358

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.6

DANN

Benign

0.48

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.45

T;T

MetaRNN

Benign

0.000048

T;T

MetaSVM

Benign

-0.90

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.040

N;N

REVEL

Benign

0.020

Sift

Benign

0.40

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.0010

.;B

Vest4

0.012

MPC

0.036

ClinPred

0.00055

GERP RS

-5.0

Varity_R

0.037

gMVP

0.19

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over