14-73949995-C-G

Position:

• chr14-73949995-C-G

Variant summary

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

The NM_182480.3(COQ6):​c.-98C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,613,392 control chromosomes in the GnomAD database, including 294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (114 hom., cov: 32)
  • Exomes 𝑓: 0.0085 (180 hom.)
• Consequence: COQ6 NM_182480.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.129

Genes affected

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]

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023985505).
• BP6: Variant 14-73949995-C-G is Benign according to our data. Variant chr14-73949995-C-G is described in ClinVar as [Benign]. Clinvar id is 1234053.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM161B	NM_152445.3	c.32G>C	p.Gly11Ala	missense_variant	1/9	ENST00000286544.5	NP_689658.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM161B	ENST00000286544.5	c.32G>C	p.Gly11Ala	missense_variant	1/9	1	NM_152445.3	ENSP00000286544.4

Frequencies

GnomAD3 genomes AF: 0.0257 AC: 3916 AN: 152156 Hom.: 114 Cov.: 32

Gnomad AFR AF: 0.0713

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0162

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0289

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00610

Gnomad OTH AF: 0.0239

GnomAD3 exomes AF: 0.0136 AC: 3400 AN: 249948 Hom.: 79 AF XY: 0.0140 AC XY: 1902 AN XY: 135468

Gnomad AFR exome AF: 0.0710

Gnomad AMR exome AF: 0.00972

Gnomad ASJ exome AF: 0.0209

Gnomad EAS exome AF: 0.000381

Gnomad SAS exome AF: 0.0305

Gnomad FIN exome AF: 0.000428

Gnomad NFE exome AF: 0.00608

Gnomad OTH exome AF: 0.0136

GnomAD4 exome AF: 0.00853 AC: 12468 AN: 1461118 Hom.: 180 Cov.: 32 AF XY: 0.00909 AC XY: 6608 AN XY: 726912

Gnomad4 AFR exome AF: 0.0725

Gnomad4 AMR exome AF: 0.0108

Gnomad4 ASJ exome AF: 0.0202

Gnomad4 EAS exome AF: 0.00108

Gnomad4 SAS exome AF: 0.0296

Gnomad4 FIN exome AF: 0.000266

Gnomad4 NFE exome AF: 0.00484

Gnomad4 OTH exome AF: 0.0141

GnomAD4 genome AF: 0.0258 AC: 3927 AN: 152274 Hom.: 114 Cov.: 32 AF XY: 0.0255 AC XY: 1896 AN XY: 74464

Gnomad4 AFR AF: 0.0713

Gnomad4 AMR AF: 0.0161

Gnomad4 ASJ AF: 0.0274

Gnomad4 EAS AF: 0.000581

Gnomad4 SAS AF: 0.0296

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00610

Gnomad4 OTH AF: 0.0251

Alfa AF: 0.0103 Hom.: 25

Bravo AF: 0.0274

TwinsUK AF: 0.00755 AC: 28

ALSPAC AF: 0.00545 AC: 21

ESP6500AA AF: 0.0642 AC: 283

ESP6500EA AF: 0.00651 AC: 56

ExAC AF: 0.0149 AC: 1814

Asia WGS AF: 0.0210 AC: 73 AN: 3478

EpiCase AF: 0.00938

EpiControl AF: 0.00782

ClinVar

Significance: Benign

Submissions summary: Benign:2

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 28, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	7.4
DANN	Benign	0.95
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.022
Sift	Benign	0.18	T
Sift4G	Benign	1.0	T
Vest4		0.11
MPC		0.074
ClinPred		0.014	T
GERP RS		1.9

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: rs11848954; hg19: chr14-74416698; COSMIC: COSV53178478; COSMIC: COSV53178478;