16-19072015-GG-AA

Variant names:

• chr16-19072015-GG-AA
• NM_016138.5:c.161_162delGGinsAA
• COQ7 p.Arg54Gln

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PS1_Moderate PP3

The NM_016138.5(COQ7):​c.161_162delGGinsAA​(p.Arg54Gln) 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely pathogenic in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R54W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: COQ7 NM_016138.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.73
• Publications: 0 publications found

Genes affected

COQ7 (HGNC:2244): (coenzyme Q7, hydroxylase) The protein encoded by this gene is similar to a mitochondrial di-iron containing hydroxylase in Saccharomyces cerevisiae that is involved with ubiquinone biosynthesis. Mutations in the yeast gene lead to slower development and longer life span. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2010]

COQ7-DT (HGNC:55362): (COQ7 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PS1: Transcript NM_016138.5 (COQ7) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.
• 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_016138.5. 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
	COQ7	NM_016138.5	MANE Select	c.161_162delGGinsAA	p.Arg54Gln	missense	N/A	NP_057222.2
	COQ7	NM_001370489.1		c.119_120delGGinsAA	p.Arg40Gln	missense	N/A	NP_001357418.1
	COQ7	NM_001370490.1		c.161_162delGGinsAA	p.Arg54Gln	missense	N/A	NP_001357419.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ7	ENST00000321998.10	TSL:1 MANE Select	c.161_162delGGinsAA	p.Arg54Gln	missense	N/A	ENSP00000322316.5	Q99807-1
	COQ7	ENST00000544894.6	TSL:1	c.47_48delGGinsAA	p.Arg16Gln	missense	N/A	ENSP00000442923.2	Q99807-2
	COQ7	ENST00000568985.5	TSL:2	c.161_162delGGinsAA	p.Arg54Gln	missense	N/A	ENSP00000456734.1	Q99807-1

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		7.7

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: chr16-19083337;