chr7-82824392-A-C
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_033026.6(PCLO):āc.14440T>Gā(p.Ser4814Ala) variant causes a missense change. The variant allele was found at a frequency of 0.432 in 1,603,872 control chromosomes in the GnomAD database, including 157,455 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.35 ( 11566 hom., cov: 29)
Exomes š: 0.44 ( 145889 hom. )
Consequence
PCLO
NM_033026.6 missense
NM_033026.6 missense
Scores
2
14
Clinical Significance
Conservation
PhyloP100: 4.23
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=6.663249E-6).
BP6
Variant 7-82824392-A-C is Benign according to our data. Variant chr7-82824392-A-C is described in ClinVar as [Benign]. Clinvar id is 1284557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-82824392-A-C is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PCLO | NM_033026.6 | c.14440T>G | p.Ser4814Ala | missense_variant | 19/25 | ENST00000333891.14 | NP_149015.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PCLO | ENST00000333891.14 | c.14440T>G | p.Ser4814Ala | missense_variant | 19/25 | 2 | NM_033026.6 | ENSP00000334319.8 | ||
PCLO | ENST00000426442.6 | n.935T>G | non_coding_transcript_exon_variant | 10/11 | 1 | |||||
PCLO | ENST00000423517.6 | c.14440T>G | p.Ser4814Ala | missense_variant | 19/20 | 5 | ENSP00000388393.2 | |||
PCLO | ENST00000618073.1 | c.703T>G | p.Ser235Ala | missense_variant | 9/10 | 5 | ENSP00000482390.1 |
Frequencies
GnomAD3 genomes AF: 0.351 AC: 53134AN: 151330Hom.: 11556 Cov.: 29
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GnomAD3 exomes AF: 0.452 AC: 111481AN: 246548Hom.: 27156 AF XY: 0.461 AC XY: 61624AN XY: 133656
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GnomAD4 exome AF: 0.440 AC: 639580AN: 1452426Hom.: 145889 Cov.: 30 AF XY: 0.445 AC XY: 321626AN XY: 722856
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GnomAD4 genome AF: 0.351 AC: 53155AN: 151446Hom.: 11566 Cov.: 29 AF XY: 0.359 AC XY: 26541AN XY: 73954
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Pontocerebellar hypoplasia type 3 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.
REVEL
Benign
Sift
Benign
T;T;.
Sift4G
Benign
T;T;T
Polyphen
0.013, 0.0
.;B;B
Vest4
MPC
ClinPred
T
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at