NM_016138.5:c.1A>C

Variant names:

• chr16-19067665-A-C
• rs1436765596
• NM_016138.5:c.1A>C

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_016138.5(COQ7):​c.1A>C​(p.Met1?) variant causes a initiator codon change involving the alteration of a non-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 Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: COQ7 NM_016138.5 initiator_codon
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 2.38
• 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 8 ACMG points.

• PVS1: Start lost variant, next in-frame start position is after 5 pathogenic variants. Next in-frame start position is after 39 codons. Genomic position: 19071969. Lost 0.176 part of the original CDS.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 16-19067665-A-C is Pathogenic according to our data. Variant chr16-19067665-A-C is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 2573010.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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ7	NM_016138.5	MANE Select	c.1A>C	p.Met1?	initiator_codon	Exon 1 of 6	NP_057222.2
	COQ7	NM_001370490.1		c.1A>C	p.Met1?	initiator_codon	Exon 1 of 5	NP_001357419.1
	COQ7-DT	NR_119379.1		n.27T>G		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.1A>C	p.Met1?	initiator_codon	Exon 1 of 6	ENSP00000322316.5	Q99807-1
	COQ7	ENST00000566110.5	TSL:4	c.-258A>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	ENSP00000456943.1	H3BSZ3
	COQ7	ENST00000568985.5	TSL:2	c.1A>C	p.Met1?	initiator_codon	Exon 1 of 7	ENSP00000456734.1	Q99807-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely pathogenic

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	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Benign	20
DANN	Benign	0.70
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.033
Eigen_PC	Benign	0.046
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Benign	-1.0	T
PhyloP100		2.4
PROVEAN	Benign	-0.50	N
REVEL	Uncertain	0.33
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.52	P
Vest4		0.90
MutPred		0.99		Loss of catalytic residue at M1 (P = 0.0059)
MVP		0.35
ClinPred		0.99	D
GERP RS		4.6
PromoterAI		0.045	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.97
gMVP		0.41

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: rs1436765596; hg19: chr16-19078987;