rs753591978

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PVS1_Moderate

The NM_182476.3(COQ6):c.1A>G(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000193 in 1,550,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

COQ6
NM_182476.3 start_lost

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.97

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PVS1

Start lost variant, next in-frame start position is after 3 pathogenic variants. Next in-frame start position is after 50 codons. Genomic position: 73950480. Lost 0.105 part of the original CDS.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COQ6	NM_182476.3	MANE Select	c.1A>G	p.Met1?	start_lost	Exon 1 of 12	NP_872282.1	Q9Y2Z9-1
COQ6	NM_001425255.1		c.1A>G	p.Met1?	start_lost	Exon 1 of 11	NP_001412184.1
COQ6	NM_001425256.1		c.1A>G	p.Met1?	start_lost	Exon 1 of 11	NP_001412185.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COQ6	ENST00000334571.7	TSL:1 MANE Select	c.1A>G	p.Met1?	start_lost	Exon 1 of 12	ENSP00000333946.2	Q9Y2Z9-1
COQ6	ENST00000554193.5	TSL:1	n.24A>G		non_coding_transcript_exon	Exon 1 of 4
COQ6	ENST00000556300.6	TSL:1	n.35A>G		non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000386

AC:

AN:

155474

AF XY:

0.0000357

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000256

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000158

Gnomad OTH exome

AF:

0.000226

GnomAD4 exome

AF:

0.0000200

AC:

AN:

1398358

Hom.:

Cov.:

AF XY:

0.0000174

AC XY:

AN XY:

691012

show subpopulations

African (AFR)

AF:

0.0000625

AC:

AN:

31998

American (AMR)

AF:

0.00

AC:

AN:

36456

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25254

East Asian (EAS)

AF:

0.000166

AC:

AN:

36252

South Asian (SAS)

AF:

0.0000874

AC:

AN:

80104

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41576

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5706

European-Non Finnish (NFE)

AF:

0.0000102

AC:

AN:

1082790

Other (OTH)

AF:

0.0000344

AC:

AN:

58222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41476

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000177

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Familial steroid-resistant nephrotic syndrome with sensorineural deafness (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.053

BayesDel_noAF

Pathogenic

0.14

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

Eigen

Benign

-0.0064

Eigen_PC

Benign

0.051

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.40

MetaRNN

Pathogenic

0.97

MetaSVM

Benign

-0.94

PhyloP100

2.0

PROVEAN

Benign

-0.65

REVEL

Benign

0.28

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.062

Vest4

0.56

MutPred

0.98

Gain of sheet (P = 0.0477)

MVP

0.34

ClinPred

1.0

GERP RS

5.2

PromoterAI

-0.45

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.97

gMVP

0.61

Mutation Taster

=23/177

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over