14-73953424-C-T

Variant names:

• chr14-73953424-C-T
• rs3213692
• NM_182476.3:c.164-11C>T

Variant summary

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

The NM_182476.3(COQ6):​c.164-11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,589,904 control chromosomes in the GnomAD database, including 32,550 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4676 hom., cov: 32)
  • Exomes 𝑓: 0.20 (27874 hom.)
• Consequence: COQ6 NM_182476.3 intron
• Scores: Splicing: ADA: 0.00001369
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.578
• Publications: 8 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]

COQ6 Gene-Disease associations (from GenCC):

• primary coenzyme Q10 deficiency 8

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• familial steroid-resistant nephrotic syndrome with sensorineural deafness

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• SMARCB1-related schwannomatosis

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 14-73953424-C-T is Benign according to our data. Variant chr14-73953424-C-T is described in ClinVar as Benign. ClinVar VariationId is 136983.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182476.3. 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_182476.3	MANE Select	c.164-11C>T		intron	N/A	NP_872282.1	Q9Y2Z9-1
	COQ6	NM_001425255.1		c.164-11C>T		intron	N/A	NP_001412184.1
	COQ6	NM_182480.3		c.89-11C>T		intron	N/A	NP_872286.2	Q9Y2Z9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ6	ENST00000334571.7	TSL:1 MANE Select	c.164-11C>T		intron	N/A	ENSP00000333946.2	Q9Y2Z9-1
	COQ6	ENST00000554193.5	TSL:1	n.187-11C>T		intron	N/A
	COQ6	ENST00000554341.6	TSL:1	n.89-11C>T		intron	N/A	ENSP00000450736.2	G3V2L5

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36317 AN: 151854 Hom.: 4666 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.210

GnomAD2 exomes AF: 0.233 AC: 57159 AN: 245772 AF XY: 0.226

Gnomad AFR exome AF: 0.303

Gnomad AMR exome AF: 0.335

Gnomad ASJ exome AF: 0.172

Gnomad EAS exome AF: 0.388

Gnomad FIN exome AF: 0.159

Gnomad NFE exome AF: 0.185

Gnomad OTH exome AF: 0.202

GnomAD4 exome AF: 0.204 AC: 292942 AN: 1437936 Hom.: 27874 Cov.: 30 AF XY: 0.204 AC XY: 145976 AN XY: 716320

African (AFR) AF: 0.305 AC: 9890 AN: 32476

American (AMR) AF: 0.335 AC: 14580 AN: 43488

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 4528 AN: 25930

East Asian (EAS) AF: 0.378 AC: 14773 AN: 39124

South Asian (SAS) AF: 0.252 AC: 21325 AN: 84734

European-Finnish (FIN) AF: 0.165 AC: 8789 AN: 53254

Middle Eastern (MID) AF: 0.150 AC: 851 AN: 5686

European-Non Finnish (NFE) AF: 0.188 AC: 205915 AN: 1093796

Other (OTH) AF: 0.207 AC: 12291 AN: 59448

GnomAD4 genome AF: 0.239 AC: 36368 AN: 151968 Hom.: 4676 Cov.: 32 AF XY: 0.238 AC XY: 17695 AN XY: 74288

African (AFR) AF: 0.314 AC: 13010 AN: 41444

American (AMR) AF: 0.256 AC: 3907 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 659 AN: 3466

East Asian (EAS) AF: 0.397 AC: 2054 AN: 5172

South Asian (SAS) AF: 0.273 AC: 1312 AN: 4812

European-Finnish (FIN) AF: 0.157 AC: 1660 AN: 10562

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13062 AN: 67960

Other (OTH) AF: 0.212 AC: 447 AN: 2108

Alfa AF: 0.0759 Hom.: 211

Bravo AF: 0.256

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.21
DANN	Benign	0.55
PhyloP100		-0.58
Mutation Taster		=52/48	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000014
dbscSNV1_RF	Benign	0.0
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: rs3213692; hg19: chr14-74420127; COSMIC: COSV53178908; COSMIC: COSV53178908;