rs575588033

Variant names:

• chr13-39655733-G-A
• rs575588033
• NM_020751.3:c.7G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-39655733-G-A
• chr13-39655733-G-C

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.7G>A​(p.Glu3Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000347 in 1,442,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E3D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: COG6 NM_020751.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.60
• 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: 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=0.12757379).

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.7G>A	p.Glu3Lys	missense	Exon 1 of 19	NP_065802.1	Q9Y2V7-1
	COG6	NM_001145079.2		c.7G>A	p.Glu3Lys	missense	Exon 1 of 19	NP_001138551.1	A0A140VJG7
	COG6	NR_026745.1		n.107G>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.7G>A	p.Glu3Lys	missense	Exon 1 of 19	ENSP00000397441.2	Q9Y2V7-1
	COG6	ENST00000416691.6	TSL:1	c.7G>A	p.Glu3Lys	missense	Exon 1 of 19	ENSP00000403733.1	Q9Y2V7-2
	COG6	ENST00000356576.8	TSL:1	n.7G>A		non_coding_transcript_exon	Exon 1 of 20	ENSP00000348983.4	Q9Y2V7-4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000347 AC: 5 AN: 1442570 Hom.: 0 Cov.: 40 AF XY: 0.00000419 AC XY: 3 AN XY: 715918

African (AFR) AF: 0.00 AC: 0 AN: 32998

American (AMR) AF: 0.00 AC: 0 AN: 43036

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25730

East Asian (EAS) AF: 0.00 AC: 0 AN: 38626

South Asian (SAS) AF: 0.00 AC: 0 AN: 83748

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51114

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5322

European-Non Finnish (NFE) AF: 0.00000454 AC: 5 AN: 1102510

Other (OTH) AF: 0.00 AC: 0 AN: 59486

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	0.0085	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0070	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.41
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.6
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.10
Sift	Benign	0.036	D
Sift4G	Benign	0.22	T
Polyphen		0.018	B
Vest4		0.24
MutPred		0.29		Gain of ubiquitination at E3 (P = 0.0045)
MVP		0.088
MPC		0.060
ClinPred		0.70	D
GERP RS		4.7
PromoterAI		-0.21	Neutral
Varity_R		0.22
gMVP		0.32
Mutation Taster		=89/11	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: rs575588033; hg19: chr13-40229870; COSMIC: COSV108171743; COSMIC: COSV108171743;