chr17-73193089-C-T

Position:

chr17-73193089-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 4P and 5B. PM1PM2BP4_StrongBP6

The NM_018714.3(COG1):c.20C>T(p.Ser7Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000788 in 1,612,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000082 ( 0 hom. )

Consequence

COG1
NM_018714.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 2.18

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 links:

ENSG00000264860 (HGNC:):

ENSG00000264860 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity COG1_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.009367824).

BP6

Variant 17-73193089-C-T is Benign according to our data. Variant chr17-73193089-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 798232.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COG1	NM_018714.3 linkuse as main transcript	c.20C>T	p.Ser7Leu	missense_variant	1/14	ENST00000299886.9	NP_061184.1	Q8WTW3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
COG1	ENST00000299886.9 linkuse as main transcript	c.20C>T	p.Ser7Leu	missense_variant	1/14	1	NM_018714.3	ENSP00000299886.4	Q8WTW3
COG1	ENST00000438720.7 linkuse as main transcript	c.17C>T	p.Ser6Leu	missense_variant	1/13	1		ENSP00000400111.3	E9PBL8
ENSG00000264860	ENST00000580671.1 linkuse as main transcript	n.502-3418C>T		intron_variant		4
COG1	ENST00000582587.2 linkuse as main transcript	n.-5C>T		upstream_gene_variant		3		ENSP00000462101.1	J3KRP4

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000211

AC:

AN:

242020

Hom.:

AF XY:

0.000219

AC XY:

AN XY:

132684

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00447

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000557

Gnomad OTH exome

AF:

0.000168

GnomAD4 exome

AF:

0.0000822

AC:

120

AN:

1460006

Hom.:

Cov.:

AF XY:

0.0000854

AC XY:

AN XY:

726344

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00349

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.0000829

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152048

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000833

Hom.:

Bravo

AF:

0.000117

ExAC

AF:

0.000141

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

COG1 congenital disorder of glycosylation

Uncertain:1Benign:1

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 13, 2023	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.011

T;T

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.036

LIST_S2

Uncertain

0.88

D;D

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.0094

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

.;L

MutationTaster

Benign

0.98

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

0.33

.;N

REVEL

Benign

0.045

Sift

Benign

0.47

.;T

Sift4G

Benign

1.0

T;T

Polyphen

0.65

.;P

Vest4

0.16

MVP

0.36

MPC

0.73

ClinPred

0.068

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.067

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over