chr13-39687808-A-G

Position:

chr13-39687808-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020751.3(COG6):c.1009+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,588,136 control chromosomes in the GnomAD database, including 52,962 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6267 hom., cov: 31)

Exomes 𝑓: 0.25 ( 46695 hom. )

Consequence

COG6
NM_020751.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0730

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 (BayesDel_noAF=-0.88).

BP6

Variant 13-39687808-A-G is Benign according to our data. Variant chr13-39687808-A-G is described in ClinVar as [Benign]. Clinvar id is 312139.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-39687808-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
COG6	NM_020751.3 linkuse as main transcript	c.1009+9A>G	intron_variant	ENST00000455146.8	NP_065802.1
COG6	NM_001145079.2 linkuse as main transcript	c.1009+9A>G	intron_variant		NP_001138551.1
COG6	XM_011535168.2 linkuse as main transcript	c.1009+9A>G	intron_variant		XP_011533470.1
COG6	NR_026745.1 linkuse as main transcript	n.1174+9A>G	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
COG6	ENST00000455146.8 linkuse as main transcript	c.1009+9A>G	intron_variant	1	NM_020751.3	ENSP00000397441	P1	Q9Y2V7-1
COG6	ENST00000416691.5 linkuse as main transcript	c.1009+9A>G	intron_variant	1		ENSP00000403733		Q9Y2V7-2
COG6	ENST00000356576.8 linkuse as main transcript	c.*846+9A>G	intron_variant, NMD_transcript_variant	1		ENSP00000348983		Q9Y2V7-4
COG6	ENST00000460701.1 linkuse as main transcript	n.257+9A>G	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

42802

AN:

151960

Hom.:

6258

Cov.:

show subpopulations

Gnomad AFR

AF:

0.367

Gnomad AMI

AF:

0.196

Gnomad AMR

AF:

0.190

Gnomad ASJ

AF:

0.240

Gnomad EAS

AF:

0.279

Gnomad SAS

AF:

0.269

Gnomad FIN

AF:

0.297

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.253

Gnomad OTH

AF:

0.273

GnomAD3 exomes

AF:

0.249

AC:

62181

AN:

249686

Hom.:

8111

AF XY:

0.250

AC XY:

33733

AN XY:

134978

show subpopulations

Gnomad AFR exome

AF:

0.369

Gnomad AMR exome

AF:

0.152

Gnomad ASJ exome

AF:

0.233

Gnomad EAS exome

AF:

0.292

Gnomad SAS exome

AF:

0.251

Gnomad FIN exome

AF:

0.293

Gnomad NFE exome

AF:

0.248

Gnomad OTH exome

AF:

0.231

GnomAD4 exome

AF:

0.253

AC:

362829

AN:

1436058

Hom.:

46695

Cov.:

AF XY:

0.252

AC XY:

180741

AN XY:

716084

show subpopulations

Gnomad4 AFR exome

AF:

0.370

Gnomad4 AMR exome

AF:

0.155

Gnomad4 ASJ exome

AF:

0.233

Gnomad4 EAS exome

AF:

0.295

Gnomad4 SAS exome

AF:

0.250

Gnomad4 FIN exome

AF:

0.289

Gnomad4 NFE exome

AF:

0.250

Gnomad4 OTH exome

AF:

0.257

GnomAD4 genome

AF:

0.282

AC:

42839

AN:

152078

Hom.:

6267

Cov.:

AF XY:

0.282

AC XY:

21002

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.367

Gnomad4 AMR

AF:

0.190

Gnomad4 ASJ

AF:

0.240

Gnomad4 EAS

AF:

0.278

Gnomad4 SAS

AF:

0.267

Gnomad4 FIN

AF:

0.297

Gnomad4 NFE

AF:

0.253

Gnomad4 OTH

AF:

0.272

Alfa

AF:

0.240

Hom.:

3465

Bravo

AF:

0.275

Asia WGS

AF:

0.290

AC:

1010

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 02, 2015	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:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

COG6-congenital disorder of glycosylation

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.81

DANN

Benign

0.54

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