chr1-234374303-TGG-GGA

Variant names:

• chr1-234374303-TGG-GGA
• NM_001206641.3:c.286_288delTGGinsGGA
• COA6 p.Trp96Gly

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM5

The NM_001206641.3(COA6):​c.286_288delTGGinsGGA​(p.Trp96Gly) variant causes a missense change. 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. W96R) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 31)
• Consequence: COA6 NM_001206641.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.50
• Publications: 0 publications found

Genes affected

COA6 (HGNC:18025): (cytochrome c oxidase assembly factor 6) This gene encodes a member of the cytochrome c oxidase subunit 6B family. The encoded protein associates with cytochrome c oxidase may act has an cytochrome c oxidase mitochondrial respiratory complex VI assembly factor. Mutations in this gene may be associated with fatal infantile cardiomyopathy. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2014]

COA6 Gene-Disease associations (from GenCC):

• cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 4

  Inheritance: AR, Unknown Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM5: Other missense variant is known to change same aminoacid residue: Variant chr1-234374303-T-C is described in ClinVar as Pathogenic. ClinVar VariationId is 204622.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206641.3. 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
	COA6	NM_001206641.3	MANE Select	c.286_288delTGGinsGGA	p.Trp96Gly	missense	N/A	NP_001193570.2	Q5JTJ3-2
	COA6	NM_001012985.2		c.196_198delTGGinsGGA	p.Trp66Gly	missense	N/A	NP_001013003.1	Q5JTJ3-1
	COA6	NM_001301733.1		c.58_60delTGGinsGGA	p.Trp20Gly	missense	N/A	NP_001288662.1	Q5JTJ3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COA6	ENST00000366615.10	TSL:1 MANE Select	c.286_288delTGGinsGGA	p.Trp96Gly	missense	N/A	ENSP00000355574.5	Q5JTJ3-2
	COA6	ENST00000366613.1	TSL:1	c.196_198delTGGinsGGA	p.Trp66Gly	missense	N/A	ENSP00000355572.1	Q5JTJ3-1
	COA6	ENST00000366612.1	TSL:1	c.58_60delTGGinsGGA	p.Trp20Gly	missense	N/A	ENSP00000355571.1	Q5JTJ3-3

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.5

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: chr1-234510049;