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: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020751.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG6	NM_020751.3	MANE Select	c.1009+9A>G		intron	N/A	NP_065802.1	Q9Y2V7-1
	COG6	NM_001145079.2		c.1009+9A>G		intron	N/A	NP_001138551.1	A0A140VJG7
	COG6	NR_026745.1		n.1174+9A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG6	ENST00000455146.8	TSL:1 MANE Select	c.1009+9A>G		intron	N/A	ENSP00000397441.2	Q9Y2V7-1
	COG6	ENST00000416691.6	TSL:1	c.1009+9A>G		intron	N/A	ENSP00000403733.1	Q9Y2V7-2
	COG6	ENST00000356576.8	TSL:1	n.*846+9A>G		intron	N/A	ENSP00000348983.4	Q9Y2V7-4

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	COG6-congenital disorder of glycosylation (1)
-	-	1	COG6-congenital disorder of glycosylation;C3809160:Hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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;