NM_016138.5:c.28_44dupCCCCGCCTTTGGCGGCT

Variant names:

• chr16-19067684-C-CGGCGGCTCCCCGCCTTT
• NM_016138.5:c.28_44dupCCCCGCCTTTGGCGGCT

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_016138.5(COQ7):​c.28_44dupCCCCGCCTTTGGCGGCT​(p.Arg16ProfsTer30) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: COQ7 NM_016138.5 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: -0.357

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

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.931 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 16-19067684-C-CGGCGGCTCCCCGCCTTT is Pathogenic according to our data. Variant chr16-19067684-C-CGGCGGCTCCCCGCCTTT is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2584462.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COQ7	NM_016138.5	c.28_44dupCCCCGCCTTTGGCGGCT	p.Arg16ProfsTer30	frameshift_variant	Exon 1 of 6	ENST00000321998.10	NP_057222.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COQ7	ENST00000321998.10	c.28_44dupCCCCGCCTTTGGCGGCT	p.Arg16ProfsTer30	frameshift_variant	Exon 1 of 6	1	NM_016138.5	ENSP00000322316.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary coenzyme Q10 deficiency 8 Pathogenic:1

-

Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This frameshifting variant in exon 1 of 6 introduces a premature stop codon and is therefore predicted to result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay (NMD). This variant has not been previously reported or functionally characterized in the literature to our knowledge; however, loss-of-function variation in COQ7 has been reported in affected individuals in the literature (PMID: 31240163). The c.28_44dup (p.Arg16ProfsTer30) variant is absent from the gnomAD population database and thus is presumed to be rare. Based on the available evidence, the c.28_44dup (p.Arg16ProfsTer30) variant is classified as Likely Pathogenic. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-19079006;