Variant 14-73950234-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000554341.6(COQ6):c.88+54G>C variant causes a intron, NMD transcript 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
ENST00000554341.6 intron, NMD_transcript

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.827

Variant links:

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]

COQ6 links:

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]

FAM161B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein
COQ6	NM_182480.3 linkuse as main transcript	c.88+54G>C	intron_variant	NP_872286.2
COQ6	XM_011536809.4 linkuse as main transcript	c.-4+54G>C	intron_variant	XP_011535111.1
COQ6	XM_047431424.1 linkuse as main transcript	c.88+54G>C	intron_variant	XP_047287380.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Protein	UniProt
COQ6	ENST00000554341.6 linkuse as main transcript	c.88+54G>C	intron_variant, NMD_transcript_variant		1	ENSP00000450736
FAM161B	ENST00000651776.1 linkuse as main transcript	c.-19C>G	5_prime_UTR_variant	1/9		ENSP00000499021	Q96MY7-2
COQ6	ENST00000394026.8 linkuse as main transcript	c.88+54G>C	intron_variant		2	ENSP00000377594	Q9Y2Z9-3

Frequencies

GnomAD3 genomes

AF:

0.0151

AC:

2303

AN:

152258

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00336

AC:

478

AN:

142288

Hom.:

AF XY:

0.00295

AC XY:

227

AN XY:

77066

show subpopulations

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 SAS exome

AF:

0.000172

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.:

Cov.:

AF XY:

0.00157

AC XY:

1075

AN XY:

684500

show subpopulations

Gnomad4 AFR exome

AF:

0.0555

Gnomad4 AMR exome

AF:

0.00330

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000100

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000275

Gnomad4 OTH exome

AF:

0.00378

GnomAD4 genome

AF:

0.0151

AC:

2307

AN:

152376

Hom.:

Cov.:

AF XY:

0.0143

AC XY:

1064

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.0521

Gnomad4 AMR

AF:

0.00510

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00718

Hom.:

Bravo

AF:

0.0172

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

7.0

DANN

Benign

0.82

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over