chr17-73200000-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_018714.3(COG1):c.1049C>T(p.Thr350Met) variant causes a missense change. The variant allele was found at a frequency of 0.00763 in 1,613,308 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0063 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0078 ( 54 hom. )

Consequence

COG1
NM_018714.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 5.63

Publications

12 publications found

Variant links:

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]

COG1 Gene-Disease associations (from GenCC):

COG1-congenital disorder of glycosylation
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet

COG1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0085653365).

BP6

Variant 17-73200000-C-T is Benign according to our data. Variant chr17-73200000-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 95910.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00628 (957/152338) while in subpopulation NFE AF = 0.0102 (693/68042). AF 95% confidence interval is 0.00956. There are 7 homozygotes in GnomAd4. There are 427 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018714.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG1	NM_018714.3	MANE Select	c.1049C>T	p.Thr350Met	missense	Exon 5 of 14	NP_061184.1	Q8WTW3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COG1	ENST00000299886.9	TSL:1 MANE Select	c.1049C>T	p.Thr350Met	missense	Exon 5 of 14	ENSP00000299886.4	Q8WTW3
COG1	ENST00000438720.7	TSL:1	c.1046C>T	p.Thr349Met	missense	Exon 5 of 13	ENSP00000400111.3	E9PBL8
COG1	ENST00000923183.1		c.1043C>T	p.Thr348Met	missense	Exon 5 of 14	ENSP00000593242.1

Frequencies

GnomAD3 genomes

AF:

0.00629

AC:

957

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00166

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.00700

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00593

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0102

Gnomad OTH

AF:

0.00623

GnomAD2 exomes

AF:

0.00529

AC:

1320

AN:

249404

AF XY:

0.00533

show subpopulations

Gnomad AFR exome

AF:

0.00138

Gnomad AMR exome

AF:

0.00248

Gnomad ASJ exome

AF:

0.000300

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00654

Gnomad NFE exome

AF:

0.00898

Gnomad OTH exome

AF:

0.00655

GnomAD4 exome

AF:

0.00777

AC:

11346

AN:

1460970

Hom.:

Cov.:

AF XY:

0.00757

AC XY:

5503

AN XY:

726722

show subpopulations

African (AFR)

AF:

0.00120

AC:

AN:

33466

American (AMR)

AF:

0.00307

AC:

137

AN:

44580

Ashkenazi Jewish (ASJ)

AF:

0.000345

AC:

AN:

26090

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.000558

AC:

AN:

86002

European-Finnish (FIN)

AF:

0.00675

AC:

360

AN:

53370

Middle Eastern (MID)

AF:

0.00538

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00929

AC:

10323

AN:

1111624

Other (OTH)

AF:

0.00659

AC:

398

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

669

1338

2008

2677

3346

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

370

740

1110

1480

1850

<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:

0.00628

AC:

957

AN:

152338

Hom.:

Cov.:

AF XY:

0.00573

AC XY:

427

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.00166

AC:

AN:

41570

American (AMR)

AF:

0.00699

AC:

107

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00593

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0102

AC:

693

AN:

68042

Other (OTH)

AF:

0.00616

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

106

160

213

266

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00815

Hom.:

Bravo

AF:

0.00646

TwinsUK

AF:

0.00917

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.00802

AC:

ExAC

AF:

0.00534

AC:

648

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (6)

not specified (3)

COG1 congenital disorder of glycosylation (2)

COG1-related disorder (1)

Intellectual disability (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.073

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.028

MetaRNN

Benign

0.0086

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.7

PhyloP100

5.6

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.25

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.018

Polyphen

1.0

Vest4

0.73

MVP

0.44

MPC

0.51

ClinPred

0.021

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

Mutation Taster

=74/26

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