rs773449359
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_006348.5(COG5):āc.2347T>Cā(p.Ser783Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,451,268 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 Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 33)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
COG5
NM_006348.5 missense
NM_006348.5 missense
Scores
1
10
8
Clinical Significance
Conservation
PhyloP100: 4.79
Genes affected
COG5 (HGNC:14857): (component of oligomeric golgi complex 5) The protein encoded by this gene is one of eight proteins (Cog1-8) which form a Golgi-localized complex (COG) required for normal Golgi morphology and function. The encoded protein is organized with conserved oligomeric Golgi complex components 6, 7 and 8 into a sub-complex referred to as lobe B. Alternative splicing results in multiple transcript variants. Mutations in this gene result in congenital disorder of glycosylation type 2I.[provided by RefSeq, Jan 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.28799063).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COG5 | NM_006348.5 | c.2347T>C | p.Ser783Pro | missense_variant | 21/22 | ENST00000297135.9 | NP_006339.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COG5 | ENST00000297135.9 | c.2347T>C | p.Ser783Pro | missense_variant | 21/22 | 1 | NM_006348.5 | ENSP00000297135 | P2 | |
COG5 | ENST00000347053.8 | c.2284T>C | p.Ser762Pro | missense_variant | 20/21 | 1 | ENSP00000334703 | A2 | ||
COG5 | ENST00000393603.7 | c.2347T>C | p.Ser783Pro | missense_variant | 21/21 | 1 | ENSP00000377228 | |||
COG5 | ENST00000464542.5 | n.798T>C | non_coding_transcript_exon_variant | 6/6 | 3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1451268Hom.: 0 Cov.: 32 AF XY: 0.00000278 AC XY: 2AN XY: 720518
GnomAD4 exome
AF:
AC:
2
AN:
1451268
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Cov.:
32
AF XY:
AC XY:
2
AN XY:
720518
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
COG5-congenital disorder of glycosylation Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 14, 2018 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with COG5-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with proline at codon 814 of the COG5 protein (p.Ser814Pro). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and proline. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
P;P;.
Vest4
MutPred
Gain of catalytic residue at P792 (P = 0.0113);.;.;
MVP
MPC
0.27
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at