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GeneBe

7-82758644-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_033026.6(PCLO):c.15360C>T(p.Asp5120=) 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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 34 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PCLONM_033026.6 linkuse as main transcriptc.15360C>T p.Asp5120= synonymous_variant 25/25 ENST00000333891.14
PCLOXM_047420210.1 linkuse as main transcriptc.15543C>T p.Asp5181= synonymous_variant 26/26
PCLOXM_047420211.1 linkuse as main transcriptc.15069C>T p.Asp5023= synonymous_variant 26/26
PCLOXM_017012006.3 linkuse as main transcriptc.8448C>T p.Asp2816= synonymous_variant 24/24

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PCLOENST00000333891.14 linkuse as main transcriptc.15360C>T p.Asp5120= synonymous_variant 25/252 NM_033026.6 P1Q9Y6V0-5

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0166
AC:
2520
AN:
151816
Hom.:
34
Cov.:
32
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.:
45
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.:
29
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0166
AC:
2525
AN:
151934
Hom.:
34
Cov.:
32
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.:
13
Bravo
AF:
0.0174
Asia WGS
AF:
0.00751
AC:
26
AN:
3478
EpiCase
AF:
0.0222
EpiControl
AF:
0.0221

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeFeb 01, 2024- -

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.

Other links and lift over

dbSNP: rs62465931; hg19: chr7-82387960; API