13-39655769-G-A

Variant names:

• chr13-39655769-G-A
• rs1023985092
• NM_020751.3:c.43G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020751.3(COG6):​c.43G>A​(p.Gly15Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,441,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: COG6 NM_020751.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.13
• 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
• hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21741635).

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.43G>A	p.Gly15Arg	missense	Exon 1 of 19	NP_065802.1	Q9Y2V7-1
	COG6	NM_001145079.2		c.43G>A	p.Gly15Arg	missense	Exon 1 of 19	NP_001138551.1	A0A140VJG7
	COG6	NR_026745.1		n.143G>A		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.43G>A	p.Gly15Arg	missense	Exon 1 of 19	ENSP00000397441.2	Q9Y2V7-1
	COG6	ENST00000416691.6	TSL:1	c.43G>A	p.Gly15Arg	missense	Exon 1 of 19	ENSP00000403733.1	Q9Y2V7-2
	COG6	ENST00000356576.8	TSL:1	n.43G>A		non_coding_transcript_exon	Exon 1 of 20	ENSP00000348983.4	Q9Y2V7-4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1441626 Hom.: 0 Cov.: 41 AF XY: 0.00000280 AC XY: 2 AN XY: 715496

African (AFR) AF: 0.00 AC: 0 AN: 32950

American (AMR) AF: 0.00 AC: 0 AN: 42916

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25776

East Asian (EAS) AF: 0.00 AC: 0 AN: 38482

South Asian (SAS) AF: 0.0000239 AC: 2 AN: 83670

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51092

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4888

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102370

Other (OTH) AF: 0.00 AC: 0 AN: 59482

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.0096	T
Eigen	Benign	0.061
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.1
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.056
Sift	Benign	0.066	T
Sift4G	Uncertain	0.036	D
Polyphen		0.78	P
Vest4		0.31
MutPred		0.33		Gain of catalytic residue at L20 (P = 0.0161)
MVP		0.17
MPC		0.38
ClinPred		0.95	D
GERP RS		5.5
PromoterAI		-0.017	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.30
Mutation Taster		=90/10	polymorphism

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: rs1023985092; hg19: chr13-40229906;