rs369616615

Variant names:

• chr16-19067673-C-A
• rs369616615
• NM_016138.5:c.9C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-19067673-C-A
• chr16-19067673-C-T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_016138.5(COQ7):​c.9C>A​(p.Cys3*) variant causes a stop gained 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 Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. C3C) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: COQ7 NM_016138.5 stop_gained
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.198
• 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: Likely_pathogenic. The variant received 6 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. There are 13 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

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.9C>A	p.Cys3*	stop_gained	Exon 1 of 6	NP_057222.2
	COQ7	NM_001370490.1		c.9C>A	p.Cys3*	stop_gained	Exon 1 of 5	NP_001357419.1
	COQ7-DT	NR_119379.1		n.19G>T		non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ7	ENST00000321998.10	TSL:1 MANE Select	c.9C>A	p.Cys3*	stop_gained	Exon 1 of 6	ENSP00000322316.5
	COQ7	ENST00000568985.5	TSL:2	c.9C>A	p.Cys3*	stop_gained	Exon 1 of 7	ENSP00000456734.1
	COQ7	ENST00000937633.1		c.9C>A	p.Cys3*	stop_gained	Exon 1 of 4	ENSP00000607692.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Primary coenzyme Q10 deficiency 8 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	34
DANN	Benign	0.94
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.060	N
PhyloP100		-0.20
Vest4		0.45
GERP RS		-4.0
PromoterAI		0.013	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs369616615; hg19: chr16-19078995;