rs17094164

Variant names:

• chr14-73950234-G-C
• rs17094164
• ENST00000554341.6:n.88+54G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_182480.3(COQ6):​c.88+54G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00307 in 1,538,710 control chromosomes in the GnomAD database, including 122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (58 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (64 hom.)
• Consequence: COQ6 NM_182480.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.827
• Publications: 2 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 14-73950234-G-C is Benign according to our data. Variant chr14-73950234-G-C is described in ClinVar as Benign. ClinVar VariationId is 1270564.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0503 is higher than 0.05.

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+54G>C		intron	N/A	NP_872286.2	Q9Y2Z9-3
	COQ6	NM_001425258.1		c.88+54G>C		intron	N/A	NP_001412187.1
	COQ6	NM_001425259.1		c.-4+54G>C		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+54G>C		intron	N/A	ENSP00000450736.2	G3V2L5
	FAM161B	ENST00000651776.1		c.-19C>G		5_prime_UTR	Exon 1 of 9	ENSP00000499021.1	Q96MY7-2
	COQ6	ENST00000394026.8	TSL:2	c.88+54G>C		intron	N/A	ENSP00000377594.4	Q9Y2Z9-3

Frequencies

GnomAD3 genomes AF: 0.0151 AC: 2303 AN: 152258 Hom.: 57 Cov.: 33

Gnomad AFR AF: 0.0522

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00510

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.0119

GnomAD2 exomes AF: 0.00336 AC: 478 AN: 142288 AF XY: 0.00295

Gnomad AFR exome AF: 0.0536

Gnomad AMR exome AF: 0.00295

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000329

Gnomad OTH exome AF: 0.00164

GnomAD4 exome AF: 0.00174 AC: 2415 AN: 1386334 Hom.: 64 Cov.: 32 AF XY: 0.00157 AC XY: 1075 AN XY: 684500

African (AFR) AF: 0.0555 AC: 1754 AN: 31618

American (AMR) AF: 0.00330 AC: 118 AN: 35782

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 35770

South Asian (SAS) AF: 0.000100 AC: 8 AN: 79816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34908

Middle Eastern (MID) AF: 0.00333 AC: 19 AN: 5698

European-Non Finnish (NFE) AF: 0.000275 AC: 297 AN: 1079582

Other (OTH) AF: 0.00378 AC: 219 AN: 57970

GnomAD4 genome AF: 0.0151 AC: 2307 AN: 152376 Hom.: 58 Cov.: 33 AF XY: 0.0143 AC XY: 1064 AN XY: 74516

African (AFR) AF: 0.0521 AC: 2167 AN: 41596

American (AMR) AF: 0.00510 AC: 78 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68036

Other (OTH) AF: 0.0118 AC: 25 AN: 2116

Alfa AF: 0.00718 Hom.: 5

Bravo AF: 0.0172

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.0
DANN	Benign	0.82
PhyloP100		0.83
PromoterAI		-0.076	Neutral
Mutation Taster		=300/0	polymorphism

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: rs17094164; hg19: chr14-74416937;