16-70512278-CTC-TTT

Variant names:

• chr16-70512278-CTC-TTT
• NM_015386.3:c.697_699delGAGinsAAA
• COG4 p.Glu233Lys

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_015386.3(COG4):​c.697_699delGAGinsAAA​(p.Glu233Lys) variant causes a missense change involving the alteration of a 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: COG4 NM_015386.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.78
• Publications: 0 publications found

Genes affected

COG4 (HGNC:18620): (component of oligomeric golgi complex 4) The protein encoded by this gene is a component of an oligomeric protein complex involved in the structure and function of the Golgi apparatus. Defects in this gene may be a cause of congenital disorder of glycosylation type IIj. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Aug 2010]

COG4 Gene-Disease associations (from GenCC):

• COG4-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• microcephalic osteodysplastic dysplasia, Saul-Wilson type

  Inheritance: AD, AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015386.3. 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
	COG4	NM_015386.3	MANE Select	c.697_699delGAGinsAAA	p.Glu233Lys	missense	N/A	NP_056201.2	J3KNI1
	COG4	NM_001195139.2		c.685_687delGAGinsAAA	p.Glu229Lys	missense	N/A	NP_001182068.2	A0A6I8PIQ6
	COG4	NM_001365426.1		c.271_273delGAGinsAAA	p.Glu91Lys	missense	N/A	NP_001352355.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG4	ENST00000323786.10	TSL:1 MANE Select	c.697_699delGAGinsAAA	p.Glu233Lys	missense	N/A	ENSP00000315775.5	J3KNI1
	COG4	ENST00000393612.8	TSL:1	c.697_699delGAGinsAAA	p.Glu233Lys	missense	N/A	ENSP00000377236.5	A0A0A0MS45
	COG4	ENST00000530314.5	TSL:1	n.610_612delGAGinsAAA		non_coding_transcript_exon	Exon 4 of 17

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.8

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: chr16-70546181;