13-39724501-TA-T

Variant names:

• chr13-39724501-TA-T
• rs66629036
• NM_020751.3:c.1693-4delA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_020751.3(COG6):​c.1693-4delA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (11154 hom., cov: 0)
  • Exomes 𝑓: 0.25 (6667 hom.)
• Consequence: COG6 NM_020751.3 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.247
• Publications: 6 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 -16 ACMG points.

• BP6: Variant 13-39724501-TA-T is Benign according to our data. Variant chr13-39724501-TA-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 95991.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.559 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.1693-4delA		splice_region intron	N/A	NP_065802.1	Q9Y2V7-1
	COG6	NM_001145079.2		c.1693-4delA		splice_region intron	N/A	NP_001138551.1	A0A140VJG7
	COG6	NR_026745.1		n.1858-4delA		splice_region intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG6	ENST00000455146.8	TSL:1 MANE Select	c.1693-6delA		splice_region intron	N/A	ENSP00000397441.2	Q9Y2V7-1
	COG6	ENST00000416691.6	TSL:1	c.1693-6delA		splice_region intron	N/A	ENSP00000403733.1	Q9Y2V7-2
	COG6	ENST00000356576.8	TSL:1	n.*1530-6delA		splice_region intron	N/A	ENSP00000348983.4	Q9Y2V7-4

Frequencies

GnomAD3 genomes AF: 0.423 AC: 55616 AN: 131480 Hom.: 11153 Cov.: 0

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.518

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.465

GnomAD2 exomes AF: 0.200 AC: 34489 AN: 172444 AF XY: 0.196

Gnomad AFR exome AF: 0.170

Gnomad AMR exome AF: 0.334

Gnomad ASJ exome AF: 0.227

Gnomad EAS exome AF: 0.236

Gnomad FIN exome AF: 0.133

Gnomad NFE exome AF: 0.161

Gnomad OTH exome AF: 0.194

GnomAD4 exome AF: 0.249 AC: 268038 AN: 1075054 Hom.: 6667 Cov.: 16 AF XY: 0.250 AC XY: 133674 AN XY: 534660

African (AFR) AF: 0.233 AC: 5646 AN: 24204

American (AMR) AF: 0.337 AC: 9131 AN: 27132

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 5355 AN: 18320

East Asian (EAS) AF: 0.322 AC: 9279 AN: 28860

South Asian (SAS) AF: 0.316 AC: 18018 AN: 56936

European-Finnish (FIN) AF: 0.181 AC: 7408 AN: 41034

Middle Eastern (MID) AF: 0.320 AC: 1003 AN: 3132

European-Non Finnish (NFE) AF: 0.241 AC: 200680 AN: 831246

Other (OTH) AF: 0.261 AC: 11518 AN: 44190

GnomAD4 genome AF: 0.423 AC: 55619 AN: 131516 Hom.: 11154 Cov.: 0 AF XY: 0.428 AC XY: 27178 AN XY: 63504

African (AFR) AF: 0.405 AC: 14314 AN: 35328

American (AMR) AF: 0.570 AC: 7588 AN: 13308

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 1556 AN: 3224

East Asian (EAS) AF: 0.518 AC: 2376 AN: 4584

South Asian (SAS) AF: 0.547 AC: 2299 AN: 4200

European-Finnish (FIN) AF: 0.346 AC: 2501 AN: 7238

Middle Eastern (MID) AF: 0.524 AC: 131 AN: 250

European-Non Finnish (NFE) AF: 0.389 AC: 23620 AN: 60704

Other (OTH) AF: 0.467 AC: 856 AN: 1832

Alfa AF: 0.329 Hom.: 219

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.25
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs66629036; hg19: chr13-40298638; COSMIC: COSV62995585;