14-73950154-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2 BP4_Strong BP6_Moderate BS1

The ENST00000554341.6(COQ6):c.62C>T(p.Ser21Phe) variant causes a missense, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000223 in 1,588,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: COQ6 ENST00000554341.6 missense, NMD_transcript
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.475

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 -8 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.004009843).
• BP6: Variant 14-73950154-C-T is Benign according to our data. Variant chr14-73950154-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1263088.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00103 (157/152390) while in subpopulation AFR AF= 0.00346 (144/41598). AF 95% confidence interval is 0.003. There are 0 homozygotes in gnomad4. There are 82 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COQ6	NM_182480.3	c.62C>T	p.Ser21Phe	missense_variant	1/12
COQ6	XM_047431424.1	c.62C>T	p.Ser21Phe	missense_variant	1/11
COQ6	XM_011536809.4	c.-30C>T		5_prime_UTR_variant	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COQ6	ENST00000554341.6	c.62C>T	p.Ser21Phe	missense_variant, NMD_transcript_variant	1/11	1
FAM161B	ENST00000651776.1	c.62G>A	p.Gly21Glu	missense_variant	1/9
COQ6	ENST00000394026.8	c.62C>T	p.Ser21Phe	missense_variant	1/12	2

Frequencies

GnomAD3 genomes AF: 0.00102 AC: 156 AN: 152272 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00345

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000347 AC: 72 AN: 207308 Hom.: 0 AF XY: 0.000270 AC XY: 31 AN XY: 114882

Gnomad AFR exome AF: 0.00445

Gnomad AMR exome AF: 0.000575

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000186

GnomAD4 exome AF: 0.000138 AC: 198 AN: 1436412 Hom.: 0 Cov.: 32 AF XY: 0.000139 AC XY: 99 AN XY: 714408

Gnomad4 AFR exome AF: 0.00443

Gnomad4 AMR exome AF: 0.000614

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000542

Gnomad4 OTH exome AF: 0.000284

GnomAD4 genome AF: 0.00103 AC: 157 AN: 152390 Hom.: 0 Cov.: 33 AF XY: 0.00110 AC XY: 82 AN XY: 74522

Gnomad4 AFR AF: 0.00346

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000623 Hom.: 0

Bravo AF: 0.00140

ExAC AF: 0.000286 AC: 34

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	6.4
Dann	Uncertain	0.99
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.0040	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.30	N
REVEL	Benign	0.0060
Sift	Pathogenic	0.0	D
Vest4		0.16
MVP		0.030
MPC		0.13
ClinPred		0.017	T
GERP RS		-3.0

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: rs73301413; hg19: chr14-74416857;