rs4129745

Variant names:

• chr13-39687808-A-G
• rs4129745
• NM_020751.3:c.1009+9A>G

Your query was ambiguous. Multiple possible variants found:

• chr13-39687808-A-G
• chr13-39687808-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• COG6-congenital disorder of glycosylation

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae)
• hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 312139.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
COG6	NM_020751.3	c.1009+9A>G		intron_variant	Intron 10 of 18	ENST00000455146.8	NP_065802.1
COG6	NM_001145079.2	c.1009+9A>G		intron_variant	Intron 10 of 18		NP_001138551.1
COG6	NR_026745.1	n.1174+9A>G		intron_variant	Intron 11 of 19
COG6	XM_011535168.2	c.1009+9A>G		intron_variant	Intron 10 of 19		XP_011533470.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG6	ENST00000455146.8	c.1009+9A>G		intron_variant	Intron 10 of 18	1	NM_020751.3	ENSP00000397441.2

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

GnomAD2 exomes AF: 0.249 AC: 62181 AN: 249686 AF XY: 0.250

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 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

African (AFR) AF: 0.370 AC: 12162 AN: 32878

American (AMR) AF: 0.155 AC: 6900 AN: 44616

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 6049 AN: 25980

East Asian (EAS) AF: 0.295 AC: 11668 AN: 39560

South Asian (SAS) AF: 0.250 AC: 21442 AN: 85644

European-Finnish (FIN) AF: 0.289 AC: 15398 AN: 53232

Middle Eastern (MID) AF: 0.215 AC: 1175 AN: 5460

European-Non Finnish (NFE) AF: 0.250 AC: 272771 AN: 1089184

Other (OTH) AF: 0.257 AC: 15264 AN: 59504

GnomAD4 genome AF: 0.282 AC: 42839 AN: 152078 Hom.: 6267 Cov.: 31 AF XY: 0.282 AC XY: 21002 AN XY: 74368

African (AFR) AF: 0.367 AC: 15218 AN: 41448

American (AMR) AF: 0.190 AC: 2907 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 833 AN: 3472

East Asian (EAS) AF: 0.278 AC: 1440 AN: 5174

South Asian (SAS) AF: 0.267 AC: 1287 AN: 4818

European-Finnish (FIN) AF: 0.297 AC: 3146 AN: 10586

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17190 AN: 67976

Other (OTH) AF: 0.272 AC: 574 AN: 2114

Alfa AF: 0.243 Hom.: 4456

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

Dec 02, 2015

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. -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

COG6-congenital disorder of glycosylation Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.81
DANN	Benign	0.54
PhyloP100		0.073
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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