13-45465041-CG-GC

Variant names:

• chr13-45465041-CG-GC
• NM_031431.4:c.5_6delCGinsGC
• COG3 p.Ala2Gly

Variant summary

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

The NM_031431.4(COG3):​c.5_6delCGinsGC​(p.Ala2Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. A2V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: COG3 NM_031431.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.39
• Publications: 0 publications found

Genes affected

COG3 (HGNC:18619): (component of oligomeric golgi complex 3) This gene encodes a component of the conserved oligomeric Golgi (COG) complex which is composed of eight different subunits and is required for normal Golgi morphology and localization. Defects in the COG complex result in multiple deficiencies in protein glycosylation. The protein encoded by this gene is involved in ER-Golgi transport.[provided by RefSeq, Jun 2011]

COG3 Gene-Disease associations (from GenCC):

• congenital disorder of glycosylation

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen
• congenital disorder of glycosylation, type IIbb

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031431.4. 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
	COG3	NM_031431.4	MANE Select	c.5_6delCGinsGC	p.Ala2Gly	missense	N/A	NP_113619.3	Q96JB2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG3	ENST00000349995.10	TSL:1 MANE Select	c.5_6delCGinsGC	p.Ala2Gly	missense	N/A	ENSP00000258654.8	Q96JB2-1
	COG3	ENST00000617493.1	TSL:1	c.5_6delCGinsGC	p.Ala2Gly	missense	N/A	ENSP00000481332.1	Q96JB2-2
	COG3	ENST00000904057.1		c.5_6delCGinsGC	p.Ala2Gly	missense	N/A	ENSP00000574116.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr13-46039176;