14-73950293-G-A

Variant names:

• chr14-73950293-G-A
• rs78801603
• ENST00000554341.6:n.88+113G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_182480.3(COQ6):​c.88+113G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: COQ6 NM_182480.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.389
• Publications: 0 publications found

Genes affected

COQ6 (HGNC:20233): (coenzyme Q6, monooxygenase) The protein encoded by this gene belongs to the ubiH/COQ6 family. It is an evolutionarily conserved monooxygenase required for the biosynthesis of coenzyme Q10 (or ubiquinone), which is an essential component of the mitochondrial electron transport chain, and one of the most potent lipophilic antioxidants implicated in the protection of cell damage by reactive oxygen species. Knockdown of this gene in mouse and zebrafish results in decreased growth due to increased apoptosis. Mutations in this gene are associated with autosomal recessive coenzyme Q10 deficiency-6 (COQ10D6), which manifests as nephrotic syndrome with sensorineural deafness. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jun 2012]

FAM161B (HGNC:19854): (FAM161 centrosomal protein B) Predicted to be involved in cilium organization. Located in cytoplasmic microtubule. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182480.3. 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
	COQ6	NM_182480.3		c.88+113G>A		intron	N/A	NP_872286.2	Q9Y2Z9-3
	COQ6	NM_001425258.1		c.88+113G>A		intron	N/A	NP_001412187.1
	COQ6	NM_001425259.1		c.-4+113G>A		intron	N/A	NP_001412188.1	A0A0D9SFJ1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ6	ENST00000554341.6	TSL:1	n.88+113G>A		intron	N/A	ENSP00000450736.2	G3V2L5
	FAM161B	ENST00000651776.1		c.-78C>T		5_prime_UTR	Exon 1 of 9	ENSP00000499021.1	Q96MY7-2
	COQ6	ENST00000963229.1		c.-40G>A		5_prime_UTR	Exon 1 of 12	ENSP00000633288.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1389310 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 685986

African (AFR) AF: 0.00 AC: 0 AN: 31710

American (AMR) AF: 0.00 AC: 0 AN: 35828

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25190

East Asian (EAS) AF: 0.00 AC: 0 AN: 35866

South Asian (SAS) AF: 0.00 AC: 0 AN: 79520

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37778

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1079718

Other (OTH) AF: 0.00 AC: 0 AN: 58002

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	4.1
DANN	Benign	0.91
PhyloP100		-0.39
PromoterAI		-0.14	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs78801603; hg19: chr14-74416996;