rs139304974
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_018714.3(COG1):c.775G>T(p.Val259Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000715 in 1,614,224 control chromosomes in the GnomAD database, including 6 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.0039 ( 3 hom., cov: 33)
Exomes 𝑓: 0.00038 ( 3 hom. )
Consequence
COG1
NM_018714.3 missense
NM_018714.3 missense
Scores
5
13
Clinical Significance
Conservation
PhyloP100: 6.27
Genes affected
COG1 (HGNC:6545): (component of oligomeric golgi complex 1) 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. It is thought that this protein is required for steps in the normal medial and trans Golgi-associated processing of glycoconjugates and plays a role in the organization of the Golgi-localized complex. [provided by RefSeq, Jul 2008]
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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=0.008938342).
BP6
Variant 17-73197258-G-T is Benign according to our data. Variant chr17-73197258-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 235502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-73197258-G-T is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00389 (592/152330) while in subpopulation AFR AF= 0.0137 (569/41572). AF 95% confidence interval is 0.0128. There are 3 homozygotes in gnomad4. There are 268 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COG1 | NM_018714.3 | c.775G>T | p.Val259Leu | missense_variant | 4/14 | ENST00000299886.9 | NP_061184.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COG1 | ENST00000299886.9 | c.775G>T | p.Val259Leu | missense_variant | 4/14 | 1 | NM_018714.3 | ENSP00000299886.4 | ||
COG1 | ENST00000438720.7 | c.772G>T | p.Val258Leu | missense_variant | 4/13 | 1 | ENSP00000400111.3 |
Frequencies
GnomAD3 genomes AF: 0.00391 AC: 595AN: 152212Hom.: 3 Cov.: 33
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GnomAD3 exomes AF: 0.000942 AC: 237AN: 251492Hom.: 2 AF XY: 0.000662 AC XY: 90AN XY: 135918
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GnomAD4 exome AF: 0.000384 AC: 562AN: 1461894Hom.: 3 Cov.: 35 AF XY: 0.000311 AC XY: 226AN XY: 727248
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GnomAD4 genome AF: 0.00389 AC: 592AN: 152330Hom.: 3 Cov.: 33 AF XY: 0.00360 AC XY: 268AN XY: 74494
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jun 04, 2015 | - - |
COG1 congenital disorder of glycosylation Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 22, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M
PrimateAI
Uncertain
T
PROVEAN
Benign
.;N
REVEL
Benign
Sift
Benign
.;T
Sift4G
Benign
T;T
Polyphen
0.13
.;B
Vest4
MutPred
Loss of glycosylation at T264 (P = 0.5412);Loss of glycosylation at T264 (P = 0.5412);
MVP
MPC
0.22
ClinPred
T
GERP RS
Varity_R
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