Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_006348.5(COG5):c.1257A>G(p.Leu419Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00324 in 1,613,526 control chromosomes in the GnomAD database, including 100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 58 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 42 hom. )

Consequence

COG5
NM_006348.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.860

Publications

6 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

COG5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 7-107298198-T-C is Benign according to our data. Variant chr7-107298198-T-C is described in ClinVar as Benign. ClinVar VariationId is 358462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.86 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0143 (2185/152284) while in subpopulation AFR AF = 0.0478 (1986/41554). AF 95% confidence interval is 0.046. There are 58 homozygotes in GnomAd4. There are 1007 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 58 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006348.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
COG5	NM_006348.5	MANE Select	c.1257A>G	p.Leu419Leu	synonymous	Exon 12 of 22	NP_006339.4
COG5	NM_181733.4		c.1257A>G	p.Leu419Leu	synonymous	Exon 12 of 21	NP_859422.3
COG5	NM_001161520.2		c.1257A>G	p.Leu419Leu	synonymous	Exon 12 of 21	NP_001154992.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
COG5	ENST00000297135.9	TSL:1 MANE Select	c.1257A>G	p.Leu419Leu	synonymous	Exon 12 of 22	ENSP00000297135.4
COG5	ENST00000347053.8	TSL:1	c.1257A>G	p.Leu419Leu	synonymous	Exon 12 of 21	ENSP00000334703.3
COG5	ENST00000393603.7	TSL:1	c.1257A>G	p.Leu419Leu	synonymous	Exon 12 of 21	ENSP00000377228.3

Frequencies

GnomAD3 genomes

AF:

0.0143

AC:

2175

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0477

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00536

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.00766

GnomAD2 exomes

AF:

0.00451

AC:

1133

AN:

251284

AF XY:

0.00368

show subpopulations

Gnomad AFR exome

AF:

0.0474

Gnomad AMR exome

AF:

0.00301

Gnomad ASJ exome

AF:

0.0151

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000713

Gnomad OTH exome

AF:

0.00392

GnomAD4 exome

AF:

0.00208

AC:

3046

AN:

1461242

Hom.:

Cov.:

AF XY:

0.00197

AC XY:

1430

AN XY:

726922

show subpopulations

African (AFR)

AF:

0.0508

AC:

1701

AN:

33458

American (AMR)

AF:

0.00356

AC:

159

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0157

AC:

409

AN:

26112

East Asian (EAS)

AF:

0.00

AC:

AN:

39634

South Asian (SAS)

AF:

0.000162

AC:

AN:

86204

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.00729

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.000349

AC:

388

AN:

1111612

Other (OTH)

AF:

0.00552

AC:

333

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

143

286

428

571

714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

204

272

340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0143

AC:

2185

AN:

152284

Hom.:

Cov.:

AF XY:

0.0135

AC XY:

1007

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0478

AC:

1986

AN:

41554

American (AMR)

AF:

0.00536

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0184

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000500

AC:

AN:

68016

Other (OTH)

AF:

0.00758

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

101

202

303

404

505

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00902

Hom.:

Bravo

AF:

0.0165

Asia WGS

AF:

0.00231

AC:

AN:

3476

EpiCase

AF:

0.00104

EpiControl

AF:

0.00113

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

COG5-congenital disorder of glycosylation (2)

COG5-related disorder (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.4

(source)

DANN

Benign

0.61

PhyloP100

-0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs74443110

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over