rs151318611

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_032382.5(COG8):c.5C>T(p.Ala2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 1,608,912 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. A2A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 4 hom. )

Consequence

COG8
NM_032382.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:6

Conservation

PhyloP100: 1.61

Publications

5 publications found

Variant links:

Genes affected

COG8 (HGNC:18623): (component of oligomeric golgi complex 8) This gene encodes a protein that is a component of the conserved oligomeric Golgi (COG) complex, a multiprotein complex that plays a structural role in the Golgi apparatus, and is involved in intracellular membrane trafficking and glycoprotein modification. Mutations in this gene cause congenital disorder of glycosylation, type IIh, a disease that is characterized by under-glycosylated serum proteins, and whose symptoms include severe psychomotor retardation, failure to thrive, seizures, and dairy and wheat product intolerance. [provided by RefSeq, Jul 2008]

COG8 links:

ENSG00000260371 (HGNC:):

ENSG00000260371 links:

NIP7 (HGNC:24328): (nucleolar pre-rRNA processing protein NIP7) Enables RNA binding activity. Predicted to be involved in ribosomal large subunit biogenesis. Located in cytosol; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NIP7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.035721958).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000847 (129/152330) while in subpopulation NFE AF = 0.00148 (101/68028). AF 95% confidence interval is 0.00125. There are 0 homozygotes in GnomAd4. There are 55 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032382.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
COG8	NM_032382.5	MANE Select	c.5C>T	p.Ala2Val	missense	Exon 1 of 6	NP_115758.3
COG8	NM_001379261.1		c.5C>T	p.Ala2Val	missense	Exon 1 of 7	NP_001366190.1
COG8	NM_001379262.1		c.5C>T	p.Ala2Val	missense	Exon 1 of 6	NP_001366191.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COG8	ENST00000306875.10	TSL:1 MANE Select	c.5C>T	p.Ala2Val	missense	Exon 1 of 6	ENSP00000305459.6	Q96MW5
ENSG00000260371	ENST00000563634.1	TSL:4	c.3-2836C>T		intron	N/A	ENSP00000454500.1	H3BMQ9
ENSG00000259900	ENST00000564737.1	TSL:5	n.466-2836C>T		intron	N/A	ENSP00000462747.1	J3KT08

Frequencies

GnomAD3 genomes

AF:

0.000848

AC:

129

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00148

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.000831

AC:

205

AN:

246564

AF XY:

0.000910

show subpopulations

Gnomad AFR exome

AF:

0.000189

Gnomad AMR exome

AF:

0.000378

Gnomad ASJ exome

AF:

0.000499

Gnomad EAS exome

AF:

0.0000550

Gnomad FIN exome

AF:

0.000930

Gnomad NFE exome

AF:

0.00138

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.00117

AC:

1705

AN:

1456582

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

850

AN XY:

724770

show subpopulations

African (AFR)

AF:

0.000180

AC:

AN:

33414

American (AMR)

AF:

0.000514

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.000306

AC:

AN:

26128

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39684

South Asian (SAS)

AF:

0.0000813

AC:

AN:

86150

European-Finnish (FIN)

AF:

0.000896

AC:

AN:

50208

Middle Eastern (MID)

AF:

0.000720

AC:

AN:

4168

European-Non Finnish (NFE)

AF:

0.00141

AC:

1568

AN:

1111932

Other (OTH)

AF:

0.000731

AC:

AN:

60186

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

193

290

386

483

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

162

216

270

<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:

0.000847

AC:

129

AN:

152330

Hom.:

Cov.:

AF XY:

0.000738

AC XY:

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41570

American (AMR)

AF:

0.000457

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000753

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00148

AC:

101

AN:

68028

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00124

Hom.:

Bravo

AF:

0.000703

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000882

AC:

107

EpiCase

AF:

0.00115

EpiControl

AF:

0.00113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

COG8-congenital disorder of glycosylation (3)

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0098

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.50

M_CAP

Benign

0.028

MetaRNN

Benign

0.036

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.69

PhyloP100

1.6

PrimateAI

Uncertain

0.57

PROVEAN

Benign

0.010

REVEL

Benign

0.12

Sift

Pathogenic

0.0

Sift4G

Benign

0.070

Polyphen

0.98

Vest4

0.53

MVP

0.65

MPC

0.93

ClinPred

0.074

GERP RS

5.2

PromoterAI

-0.39

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.25

gMVP

0.62

Mutation Taster

=77/23

polymorphism

(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

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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

Computational scores

Splicing

Publications

Other links and lift over