rs886050223

Variant names:

• chr13-39655738-C-T
• rs886050223
• NM_020751.3:c.12C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_020751.3(COG6):​c.12C>T​(p.Gly4Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: COG6 NM_020751.3 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.692
• Publications: 0 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, PanelApp Australia
• hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP7: Synonymous conserved (PhyloP=-0.692 with no splicing effect.

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.12C>T	p.Gly4Gly	synonymous	Exon 1 of 19	NP_065802.1	Q9Y2V7-1
	COG6	NM_001145079.2		c.12C>T	p.Gly4Gly	synonymous	Exon 1 of 19	NP_001138551.1	A0A140VJG7
	COG6	NR_026745.1		n.112C>T		non_coding_transcript_exon	Exon 1 of 20

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG6	ENST00000455146.8	TSL:1 MANE Select	c.12C>T	p.Gly4Gly	synonymous	Exon 1 of 19	ENSP00000397441.2	Q9Y2V7-1
	COG6	ENST00000416691.6	TSL:1	c.12C>T	p.Gly4Gly	synonymous	Exon 1 of 19	ENSP00000403733.1	Q9Y2V7-2
	COG6	ENST00000356576.8	TSL:1	n.12C>T		non_coding_transcript_exon	Exon 1 of 20	ENSP00000348983.4	Q9Y2V7-4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1443662 Hom.: 0 Cov.: 39 AF XY: 0.00 AC XY: 0 AN XY: 716580

African (AFR) AF: 0.00 AC: 0 AN: 33036

American (AMR) AF: 0.00 AC: 0 AN: 43142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25738

East Asian (EAS) AF: 0.00 AC: 0 AN: 38704

South Asian (SAS) AF: 0.00 AC: 0 AN: 83886

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51134

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5282

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1103194

Other (OTH) AF: 0.00 AC: 0 AN: 59546

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	COG6-congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	10
DANN	Benign	0.89
PhyloP100		-0.69
PromoterAI		-0.011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs886050223; hg19: chr13-40229875;