Variant 7-82758644-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_033026.6(PCLO):c.15360C>T(p.Asp5120Asp) variant causes a synonymous change. The variant allele was found at a frequency of 0.0195 in 1,611,034 control chromosomes in the GnomAD database, including 358 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 34 hom., cov: 32)

Exomes 𝑓: 0.020 ( 324 hom. )

Consequence

PCLO
NM_033026.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.33

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 7-82758644-G-A is Benign according to our data. Variant chr7-82758644-G-A is described in ClinVar as [Benign]. Clinvar id is 1600328.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0166 (2525/151934) while in subpopulation NFE AF= 0.021 (1427/67864). AF 95% confidence interval is 0.0201. There are 34 homozygotes in gnomad4. There are 1106 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 34 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PCLO	NM_033026.6 linkuse as main transcript	c.15360C>T	p.Asp5120Asp	synonymous_variant	25/25	ENST00000333891.14	NP_149015.2
PCLO	XM_047420210.1 linkuse as main transcript	c.15543C>T	p.Asp5181Asp	synonymous_variant	26/26		XP_047276166.1
PCLO	XM_047420211.1 linkuse as main transcript	c.15069C>T	p.Asp5023Asp	synonymous_variant	26/26		XP_047276167.1
PCLO	XM_017012006.3 linkuse as main transcript	c.8448C>T	p.Asp2816Asp	synonymous_variant	24/24		XP_016867495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCLO	ENST00000333891.14 linkuse as main transcript	c.15360C>T	p.Asp5120Asp	synonymous_variant	25/25	2	NM_033026.6	ENSP00000334319.8		Q9Y6V0-5

Frequencies

GnomAD3 genomes

AF:

0.0166

AC:

2520

AN:

151816

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0150

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.0105

Gnomad ASJ

AF:

0.0300

Gnomad EAS

AF:

0.00425

Gnomad SAS

AF:

0.0128

Gnomad FIN

AF:

0.00264

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0210

Gnomad OTH

AF:

0.0206

GnomAD3 exomes

AF:

0.0161

AC:

4011

AN:

248534

Hom.:

AF XY:

0.0166

AC XY:

2238

AN XY:

134838

show subpopulations

Gnomad AFR exome

AF:

0.0166

Gnomad AMR exome

AF:

0.0100

Gnomad ASJ exome

AF:

0.0277

Gnomad EAS exome

AF:

0.00300

Gnomad SAS exome

AF:

0.0124

Gnomad FIN exome

AF:

0.00377

Gnomad NFE exome

AF:

0.0222

Gnomad OTH exome

AF:

0.0199

GnomAD4 exome

AF:

0.0198

AC:

28828

AN:

1459100

Hom.:

324

Cov.:

AF XY:

0.0195

AC XY:

14154

AN XY:

725968

show subpopulations

Gnomad4 AFR exome

AF:

0.0165

Gnomad4 AMR exome

AF:

0.00981

Gnomad4 ASJ exome

AF:

0.0285

Gnomad4 EAS exome

AF:

0.00356

Gnomad4 SAS exome

AF:

0.0118

Gnomad4 FIN exome

AF:

0.00495

Gnomad4 NFE exome

AF:

0.0219

Gnomad4 OTH exome

AF:

0.0202

GnomAD4 genome

AF:

0.0166

AC:

2525

AN:

151934

Hom.:

Cov.:

AF XY:

0.0149

AC XY:

1106

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.0150

Gnomad4 AMR

AF:

0.0105

Gnomad4 ASJ

AF:

0.0300

Gnomad4 EAS

AF:

0.00407

Gnomad4 SAS

AF:

0.0133

Gnomad4 FIN

AF:

0.00264

Gnomad4 NFE

AF:

0.0210

Gnomad4 OTH

AF:

0.0204

Alfa

AF:

0.0202

Hom.:

Bravo

AF:

0.0174

Asia WGS

AF:

0.00751

AC:

AN:

3478

EpiCase

AF:

0.0222

EpiControl

AF:

0.0221

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

BayesDel_noAF

Benign

-0.40

CADD

Benign

5.3

DANN

Benign

0.66

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