NM_006348.5:c.2347T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006348.5(COG5):​c.2347T>G​(p.Ser783Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,451,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S783P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

COG5
NM_006348.5 missense

Scores

5
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.79

Publications

0 publications found
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]
COG5 Gene-Disease associations (from GenCC):
  • COG5-congenital disorder of glycosylation
    Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Laboratory for Molecular Medicine, Orphanet, G2P

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15770146).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COG5NM_006348.5 linkc.2347T>G p.Ser783Ala missense_variant Exon 21 of 22 ENST00000297135.9 NP_006339.4 Q9UP83

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COG5ENST00000297135.9 linkc.2347T>G p.Ser783Ala missense_variant Exon 21 of 22 1 NM_006348.5 ENSP00000297135.4 Q9UP83
COG5ENST00000347053.8 linkc.2284T>G p.Ser762Ala missense_variant Exon 20 of 21 1 ENSP00000334703.3 Q9UP83
COG5ENST00000393603.7 linkc.2347T>G p.Ser783Ala missense_variant Exon 21 of 21 1 ENSP00000377228.3 Q9UP83
COG5ENST00000464542.5 linkn.798T>G non_coding_transcript_exon_variant Exon 6 of 6 3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.89e-7
AC:
1
AN:
1451268
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
720518
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
33418
American (AMR)
AF:
0.00
AC:
0
AN:
43326
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25812
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39560
South Asian (SAS)
AF:
0.00
AC:
0
AN:
83766
European-Finnish (FIN)
AF:
0.0000190
AC:
1
AN:
52614
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5506
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1107246
Other (OTH)
AF:
0.00
AC:
0
AN:
60020
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.066
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.011
T;.;.
Eigen
Benign
-0.055
Eigen_PC
Benign
0.072
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.68
T;T;T
M_CAP
Benign
0.0068
T
MetaRNN
Benign
0.16
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.1
M;.;.
PhyloP100
4.8
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-1.9
N;N;N
REVEL
Benign
0.063
Sift
Uncertain
0.021
D;D;D
Sift4G
Benign
0.074
T;T;T
Polyphen
0.0090
B;B;.
Vest4
0.31
MutPred
0.20
Loss of disorder (P = 0.0649);.;.;
MVP
0.42
MPC
0.050
ClinPred
0.97
D
GERP RS
4.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.28
gMVP
0.25
Mutation Taster
=86/14
polymorphism

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

Other links and lift over

dbSNP: rs773449359; hg19: chr7-106850999; API