chr14-73950293-G-T

Variant names:

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

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+113G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00473 in 1,541,696 control chromosomes in the GnomAD database, including 293 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (142 hom., cov: 33)
  • Exomes 𝑓: 0.0026 (151 hom.)
• Consequence: COQ6 NM_182480.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.389
• Publications: 3 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=-0.72).
• BP6: Variant 14-73950293-G-T is Benign according to our data. Variant chr14-73950293-G-T is described in ClinVar as Benign. ClinVar VariationId is 136987.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0821 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+113G>T		intron	N/A	NP_872286.2	Q9Y2Z9-3
	COQ6	NM_001425258.1		c.88+113G>T		intron	N/A	NP_001412187.1
	COQ6	NM_001425259.1		c.-4+113G>T		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>T		intron	N/A	ENSP00000450736.2	G3V2L5
	FAM161B	ENST00000651776.1		c.-78C>A		5_prime_UTR	Exon 1 of 9	ENSP00000499021.1	Q96MY7-2
	COQ6	ENST00000963229.1		c.-40G>T		5_prime_UTR	Exon 1 of 12	ENSP00000633288.1

Frequencies

GnomAD3 genomes AF: 0.0243 AC: 3702 AN: 152270 Hom.: 141 Cov.: 33

Gnomad AFR AF: 0.0845

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00863

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.0186

GnomAD2 exomes AF: 0.00619 AC: 907 AN: 146580 AF XY: 0.00455

Gnomad AFR exome AF: 0.0984

Gnomad AMR exome AF: 0.00404

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000455

Gnomad OTH exome AF: 0.00325

GnomAD4 exome AF: 0.00258 AC: 3584 AN: 1389310 Hom.: 151 Cov.: 32 AF XY: 0.00221 AC XY: 1515 AN XY: 685986

African (AFR) AF: 0.0912 AC: 2893 AN: 31710

American (AMR) AF: 0.00463 AC: 166 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: 0.0000755 AC: 6 AN: 79520

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

Middle Eastern (MID) AF: 0.00421 AC: 24 AN: 5698

European-Non Finnish (NFE) AF: 0.000174 AC: 188 AN: 1079718

Other (OTH) AF: 0.00529 AC: 307 AN: 58002

GnomAD4 genome AF: 0.0243 AC: 3709 AN: 152386 Hom.: 142 Cov.: 33 AF XY: 0.0225 AC XY: 1673 AN XY: 74520

African (AFR) AF: 0.0844 AC: 3510 AN: 41590

American (AMR) AF: 0.00862 AC: 132 AN: 15312

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000367 AC: 25 AN: 68044

Other (OTH) AF: 0.0184 AC: 39 AN: 2116

Alfa AF: 0.0105 Hom.: 25

Bravo AF: 0.0282

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.6
DANN	Benign	0.77
PhyloP100		-0.39
PromoterAI		-0.17	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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;