7-107362380-A-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_006348.5(COG5):ā€‹c.876T>Gā€‹(p.Thr292=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,613,910 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.0085 ( 23 hom., cov: 32)
Exomes š‘“: 0.0010 ( 15 hom. )

Consequence

COG5
NM_006348.5 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0350
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 Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
Variant 7-107362380-A-C is Benign according to our data. Variant chr7-107362380-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 358465.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.035 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00849 (1293/152300) while in subpopulation AFR AF= 0.0284 (1179/41554). AF 95% confidence interval is 0.027. There are 23 homozygotes in gnomad4. There are 630 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COG5NM_006348.5 linkuse as main transcriptc.876T>G p.Thr292= synonymous_variant 9/22 ENST00000297135.9 NP_006339.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
COG5ENST00000297135.9 linkuse as main transcriptc.876T>G p.Thr292= synonymous_variant 9/221 NM_006348.5 ENSP00000297135 P2
COG5ENST00000347053.8 linkuse as main transcriptc.876T>G p.Thr292= synonymous_variant 9/211 ENSP00000334703 A2
COG5ENST00000393603.7 linkuse as main transcriptc.876T>G p.Thr292= synonymous_variant 9/211 ENSP00000377228
COG5ENST00000484237.5 linkuse as main transcriptn.459T>G non_coding_transcript_exon_variant 4/54

Frequencies

GnomAD3 genomes
AF:
0.00848
AC:
1290
AN:
152182
Hom.:
23
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0284
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00452
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.000397
Gnomad OTH
AF:
0.00767
GnomAD3 exomes
AF:
0.00235
AC:
592
AN:
251444
Hom.:
7
AF XY:
0.00181
AC XY:
246
AN XY:
135904
show subpopulations
Gnomad AFR exome
AF:
0.0297
Gnomad AMR exome
AF:
0.00205
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:
0.000255
Gnomad OTH exome
AF:
0.00147
GnomAD4 exome
AF:
0.00103
AC:
1509
AN:
1461610
Hom.:
15
Cov.:
33
AF XY:
0.000909
AC XY:
661
AN XY:
727128
show subpopulations
Gnomad4 AFR exome
AF:
0.0289
Gnomad4 AMR exome
AF:
0.00239
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000228
Gnomad4 OTH exome
AF:
0.00272
GnomAD4 genome
AF:
0.00849
AC:
1293
AN:
152300
Hom.:
23
Cov.:
32
AF XY:
0.00846
AC XY:
630
AN XY:
74480
show subpopulations
Gnomad4 AFR
AF:
0.0284
Gnomad4 AMR
AF:
0.00451
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000382
Gnomad4 OTH
AF:
0.00759
Alfa
AF:
0.00452
Hom.:
2
Bravo
AF:
0.00986
Asia WGS
AF:
0.00520
AC:
18
AN:
3478
EpiCase
AF:
0.000327
EpiControl
AF:
0.000296

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

COG5-congenital disorder of glycosylation Benign:2
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxAug 02, 2016This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
COG5-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesOct 23, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.53
CADD
Benign
7.0
DANN
Benign
0.61
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs74522314; hg19: chr7-107002825; API