13-39687612-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_020751.3(COG6):c.898C>T(p.His300Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00231 in 1,613,904 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 40 hom., cov: 31)

Exomes 𝑓: 0.0013 ( 26 hom. )

Consequence

COG6
NM_020751.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 5.63

Variant links:

Genes affected

COG6 (HGNC:18621): (component of oligomeric golgi complex 6) This gene encodes a subunit of the conserved oligomeric Golgi complex that is required for maintaining normal structure and activity of the Golgi apparatus. The encoded protein is organized with conserved oligomeric Golgi complex components 5, 7 and 8 into a sub-complex referred to as lobe B. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Feb 2009]

COG6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00874576).

BP6

Variant 13-39687612-C-T is Benign according to our data. Variant chr13-39687612-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 166919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0124 (1886/152048) while in subpopulation AFR AF= 0.0431 (1787/41446). AF 95% confidence interval is 0.0415. There are 40 homozygotes in gnomad4. There are 865 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 40 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG6	NM_020751.3 link	c.898C>T	p.His300Tyr	missense_variant	Exon 9 of 19	ENST00000455146.8	NP_065802.1	Q9Y2V7-1A0A024RDW5
COG6	NM_001145079.2 link	c.898C>T	p.His300Tyr	missense_variant	Exon 9 of 19		NP_001138551.1	Q9Y2V7-2A0A140VJG7
COG6	XM_011535168.2 link	c.898C>T	p.His300Tyr	missense_variant	Exon 9 of 20		XP_011533470.1
COG6	NR_026745.1 link	n.1063C>T		non_coding_transcript_exon_variant	Exon 10 of 20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG6	ENST00000455146.8 link	c.898C>T	p.His300Tyr	missense_variant	Exon 9 of 19	1	NM_020751.3	ENSP00000397441.2		Q9Y2V7-1

Frequencies

GnomAD3 genomes

AF:

0.0124

AC:

1879

AN:

151930

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0430

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00472

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00319

AC:

803

AN:

251426

Hom.:

AF XY:

0.00241

AC XY:

328

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.0444

Gnomad AMR exome

AF:

0.00162

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:

0.000106

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00126

AC:

1839

AN:

1461856

Hom.:

Cov.:

AF XY:

0.00111

AC XY:

807

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.0457

Gnomad4 AMR exome

AF:

0.00188

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000234

Gnomad4 OTH exome

AF:

0.00305

GnomAD4 genome

AF:

0.0124

AC:

1886

AN:

152048

Hom.:

Cov.:

AF XY:

0.0116

AC XY:

865

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0431

Gnomad4 AMR

AF:

0.00465

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00242

Hom.:

Bravo

AF:

0.0144

ESP6500AA

AF:

0.0413

AC:

182

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00411

AC:

499

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 17, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 03, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This 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. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 30, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

COG6-congenital disorder of glycosylation;C3809160:Hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome

Benign:2

Dec 02, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 13, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

COG6-congenital disorder of glycosylation

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

.;T

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

D;D

MetaRNN

Benign

0.0087

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.1

M;M

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-3.4

D;D

REVEL

Benign

0.16

Sift

Benign

0.14

T;T

Sift4G

Uncertain

0.054

T;T

Polyphen

0.42

.;B

Vest4

0.68

MVP

0.49

MPC

0.067

ClinPred

0.080

GERP RS

5.6

Varity_R

0.46

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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