chr14-73950242-G-C

Variant names:

Variant summary

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

The NM_182480.3(COQ6):c.88+62G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,538,458 control chromosomes in the GnomAD database, including 17,104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1279 hom., cov: 33)

Exomes 𝑓: 0.15 ( 15825 hom. )

Consequence

COQ6
NM_182480.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.15

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=-0.76).

BP6

Variant 14-73950242-G-C is Benign according to our data. Variant chr14-73950242-G-C is described in ClinVar as [Benign]. Clinvar id is 1291437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-73950242-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM161B	NM_152445.3 link	c.-216C>G		upstream_gene_variant		ENST00000286544.5	NP_689658.3	Q96MY7-1
COQ6	NM_182476.3 link	c.-91G>C		upstream_gene_variant		ENST00000334571.7	NP_872282.1	Q9Y2Z9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM161B	ENST00000286544.5 link	c.-216C>G		upstream_gene_variant		1	NM_152445.3	ENSP00000286544.4		Q96MY7-1
COQ6	ENST00000334571.7 link	c.-91G>C		upstream_gene_variant		1	NM_182476.3	ENSP00000333946.2		Q9Y2Z9-1

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

17305

AN:

152238

Hom.:

1278

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0285

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.192

Gnomad ASJ

AF:

0.133

Gnomad EAS

AF:

0.0774

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.147

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.145

Gnomad OTH

AF:

0.112

GnomAD3 exomes

AF:

0.156

AC:

22237

AN:

142360

Hom.:

2263

AF XY:

0.151

AC XY:

11579

AN XY:

76932

show subpopulations

Gnomad AFR exome

AF:

0.0266

Gnomad AMR exome

AF:

0.297

Gnomad ASJ exome

AF:

0.128

Gnomad EAS exome

AF:

0.0685

Gnomad SAS exome

AF:

0.120

Gnomad FIN exome

AF:

0.152

Gnomad NFE exome

AF:

0.148

Gnomad OTH exome

AF:

0.146

GnomAD4 exome

AF:

0.145

AC:

201255

AN:

1386100

Hom.:

15825

Cov.:

AF XY:

0.144

AC XY:

98387

AN XY:

684284

show subpopulations

Gnomad4 AFR exome

AF:

0.0229

Gnomad4 AMR exome

AF:

0.281

Gnomad4 ASJ exome

AF:

0.131

Gnomad4 EAS exome

AF:

0.0790

Gnomad4 SAS exome

AF:

0.115

Gnomad4 FIN exome

AF:

0.152

Gnomad4 NFE exome

AF:

0.150

Gnomad4 OTH exome

AF:

0.136

GnomAD4 genome

AF:

0.114

AC:

17307

AN:

152358

Hom.:

1279

Cov.:

AF XY:

0.114

AC XY:

8459

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.0285

Gnomad4 AMR

AF:

0.192

Gnomad4 ASJ

AF:

0.133

Gnomad4 EAS

AF:

0.0778

Gnomad4 SAS

AF:

0.116

Gnomad4 FIN

AF:

0.147

Gnomad4 NFE

AF:

0.145

Gnomad4 OTH

AF:

0.110

Alfa

AF:

0.136

Hom.:

312

Bravo

AF:

0.119

Asia WGS

AF:

0.0760

AC:

265

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 37% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 34. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

1.0

DANN

Benign

0.71

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