rs4129745

Positions:

• chr13-39687808-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0730

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]

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COG6	NM_020751.3	c.1009+9A>G		intron_variant		ENST00000455146.8	NP_065802.1
COG6	NM_001145079.2	c.1009+9A>G		intron_variant			NP_001138551.1
COG6	XM_011535168.2	c.1009+9A>G		intron_variant			XP_011533470.1
COG6	NR_026745.1	n.1174+9A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COG6	ENST00000455146.8	c.1009+9A>G		intron_variant		1	NM_020751.3	ENSP00000397441	P1
COG6	ENST00000416691.5	c.1009+9A>G		intron_variant		1		ENSP00000403733
COG6	ENST00000356576.8	c.*846+9A>G		intron_variant, NMD_transcript_variant		1		ENSP00000348983
COG6	ENST00000460701.1	n.257+9A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42802 AN: 151960 Hom.: 6258 Cov.: 31

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

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.: 27 AF XY: 0.252 AC XY: 180741 AN XY: 716084

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.: 31 AF XY: 0.282 AC XY: 21002 AN XY: 74368

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

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

Other links and lift over

dbSNP: rs4129745; hg19: chr13-40261945; COSMIC: COSV104414827; COSMIC: COSV104414827;