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GeneBe

12-54349649-C-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_016057.3(COPZ1):c.477C>A(p.Thr159=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000274 in 1,612,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

COPZ1
NM_016057.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.64
Variant links:
Genes affected
COPZ1 (HGNC:2243): (COPI coat complex subunit zeta 1) This gene encodes a subunit of the cytoplasmic coatamer protein complex, which is involved in autophagy and intracellular protein trafficking. The coatomer protein complex is comprised of seven subunits and functions as the coat protein of coat protein complex (COP)I-vesicles. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
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=-0.52).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-54349649-C-A is Benign according to our data. Variant chr12-54349649-C-A is described in ClinVar as [Benign]. Clinvar id is 746724.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.64 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
COPZ1NM_016057.3 linkuse as main transcriptc.477C>A p.Thr159= synonymous_variant 8/9 ENST00000262061.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
COPZ1ENST00000262061.7 linkuse as main transcriptc.477C>A p.Thr159= synonymous_variant 8/91 NM_016057.3 P1P61923-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00139
AC:
212
AN:
152192
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00468
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000916
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.000398
AC:
100
AN:
251486
Hom.:
0
AF XY:
0.000353
AC XY:
48
AN XY:
135916
show subpopulations
Gnomad AFR exome
AF:
0.00498
Gnomad AMR exome
AF:
0.000463
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000155
AC:
227
AN:
1460208
Hom.:
0
Cov.:
29
AF XY:
0.000167
AC XY:
121
AN XY:
726524
show subpopulations
Gnomad4 AFR exome
AF:
0.00476
Gnomad4 AMR exome
AF:
0.000492
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000810
Gnomad4 OTH exome
AF:
0.000514
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00141
AC:
215
AN:
152310
Hom.:
0
Cov.:
32
AF XY:
0.00129
AC XY:
96
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.00474
Gnomad4 AMR
AF:
0.000915
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000176
Hom.:
0
Bravo
AF:
0.00166
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 testingInvitaeDec 13, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.52
Cadd
Benign
0.24
Dann
Benign
0.74
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.6

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs115975751; hg19: chr12-54743433; API