rs864321686

Variant names:

• chr16-19075775-T-A
• rs864321686
• NM_016138.5:c.422T>A

Your query was ambiguous. Multiple possible variants found:

• chr16-19075775-T-A
• chr16-19075775-T-G

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PM2 PP3_Strong PP5_Moderate

The NM_016138.5(COQ7):​c.422T>A​(p.Val141Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V141M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: COQ7 NM_016138.5 missense
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 7.70
• Publications: 19 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 8 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.953
• PP5: Variant 16-19075775-T-A is Pathogenic according to our data. Variant chr16-19075775-T-A is described in ClinVar as Pathogenic. ClinVar VariationId is 219119.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ7	NM_016138.5	MANE Select	c.422T>A	p.Val141Glu	missense	Exon 4 of 6	NP_057222.2
	COQ7	NM_001370489.1		c.380T>A	p.Val127Glu	missense	Exon 4 of 6	NP_001357418.1
	COQ7	NM_001370490.1		c.422T>A	p.Val141Glu	missense	Exon 4 of 5	NP_001357419.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ7	ENST00000321998.10	TSL:1 MANE Select	c.422T>A	p.Val141Glu	missense	Exon 4 of 6	ENSP00000322316.5
	COQ7	ENST00000544894.6	TSL:1	c.308T>A	p.Val103Glu	missense	Exon 4 of 6	ENSP00000442923.2
	COQ7	ENST00000568985.5	TSL:2	c.422T>A	p.Val141Glu	missense	Exon 4 of 7	ENSP00000456734.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
2	-	-	Primary coenzyme Q10 deficiency 8 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.73	D
Eigen	Pathogenic	0.95
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Uncertain	0.24	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Uncertain	0.34	D
MutationAssessor	Pathogenic	3.9	H
PhyloP100		7.7
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Pathogenic	0.81
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.89
MutPred		0.80		Gain of disorder (P = 0.0022)
MVP		0.86
MPC		0.52
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.97
gMVP		0.96
Mutation Taster		=0/100	disease causing (ClinVar)

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: rs864321686; hg19: chr16-19087097;