rs17552038

Positions:

• chr14-73950242-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000554341.6(COQ6):​c.88+62G>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 0.142 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 ENST00000554341.6 intron, NMD_transcript
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.15

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

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/exons	MANE	Protein	UniProt
COQ6	NM_182480.3	c.88+62G>C		intron_variant			NP_872286.2
COQ6	XM_011536809.4	c.-4+62G>C		intron_variant			XP_011535111.1
COQ6	XM_047431424.1	c.88+62G>C		intron_variant			XP_047287380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COQ6	ENST00000554341.6	c.88+62G>C		intron_variant, NMD_transcript_variant		1		ENSP00000450736
FAM161B	ENST00000651776.1	c.-27C>G		5_prime_UTR_variant	1/9			ENSP00000499021
COQ6	ENST00000394026.8	c.88+62G>C		intron_variant		2		ENSP00000377594

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17305 AN: 152238 Hom.: 1278 Cov.: 33

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

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.: 33 AF XY: 0.144 AC XY: 98387 AN XY: 684284

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.: 33 AF XY: 0.114 AC XY: 8459 AN XY: 74516

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

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	Jun 23, 2018	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 15, 2024

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

Other links and lift over

dbSNP: rs17552038; hg19: chr14-74416945; COSMIC: COSV53178557; COSMIC: COSV53178557;