rs773449359

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006348.5(COG5):ā€‹c.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

Scores

1
10
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.79
Variant links:
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
COG5NM_006348.5 linkuse as main transcriptc.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
COG5ENST00000297135.9 linkuse as main transcriptc.2347T>C p.Ser783Pro missense_variant 21/221 NM_006348.5 ENSP00000297135 P2
COG5ENST00000347053.8 linkuse as main transcriptc.2284T>C p.Ser762Pro missense_variant 20/211 ENSP00000334703 A2
COG5ENST00000393603.7 linkuse as main transcriptc.2347T>C p.Ser783Pro missense_variant 21/211 ENSP00000377228
COG5ENST00000464542.5 linkuse as main transcriptn.798T>C non_coding_transcript_exon_variant 6/63

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000138
AC:
2
AN:
1451268
Hom.:
0
Cov.:
32
AF XY:
0.00000278
AC XY:
2
AN XY:
720518
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000181
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJun 14, 2018In 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.56
BayesDel_addAF
Benign
-0.054
T
BayesDel_noAF
Benign
-0.32
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.085
T;.;.
Eigen
Uncertain
0.40
Eigen_PC
Uncertain
0.39
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.90
D;D;D
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.29
T;T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Uncertain
2.7
M;.;.
MutationTaster
Benign
0.98
D;D;D
PrimateAI
Uncertain
0.54
T
PROVEAN
Uncertain
-3.2
D;D;D
REVEL
Benign
0.13
Sift
Uncertain
0.011
D;D;D
Sift4G
Uncertain
0.025
D;D;D
Polyphen
0.83
P;P;.
Vest4
0.62
MutPred
0.30
Gain of catalytic residue at P792 (P = 0.0113);.;.;
MVP
0.46
MPC
0.27
ClinPred
0.99
D
GERP RS
4.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.57
gMVP
0.62

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: rs773449359; hg19: chr7-106850999; API