chr16-19067684-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting

The NM_016138.5(COQ7):c.20C>T(p.Ala7Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000077 in 1,610,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A7P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000078 ( 0 hom. )

Consequence

COQ7
NM_016138.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.406

Publications

0 publications found

Variant links:

Genes affected

COQ7 (HGNC:2244): (coenzyme Q7, hydroxylase) The protein encoded by this gene is similar to a mitochondrial di-iron containing hydroxylase in Saccharomyces cerevisiae that is involved with ubiquinone biosynthesis. Mutations in the yeast gene lead to slower development and longer life span. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2010]

COQ7 links:

COQ7-DT (HGNC:55362): (COQ7 divergent transcript)

COQ7-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016327739).

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0000656 (10/152328) while in subpopulation AMR AF = 0.000261 (4/15306). AF 95% confidence interval is 0.0000887. There are 0 homozygotes in GnomAd4. There are 4 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016138.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
COQ7	NM_016138.5	MANE Select	c.20C>T	p.Ala7Val	missense	Exon 1 of 6	NP_057222.2
COQ7	NM_001370490.1		c.20C>T	p.Ala7Val	missense	Exon 1 of 5	NP_001357419.1
COQ7-DT	NR_119379.1		n.8G>A		non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COQ7	ENST00000321998.10	TSL:1 MANE Select	c.20C>T	p.Ala7Val	missense	Exon 1 of 6	ENSP00000322316.5	Q99807-1
COQ7	ENST00000568985.5	TSL:2	c.20C>T	p.Ala7Val	missense	Exon 1 of 7	ENSP00000456734.1	Q99807-1
COQ7	ENST00000937633.1		c.20C>T	p.Ala7Val	missense	Exon 1 of 4	ENSP00000607692.1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000205

AC:

AN:

238884

AF XY:

0.000153

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00127

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000472

Gnomad OTH exome

AF:

0.000171

GnomAD4 exome

AF:

0.0000782

AC:

114

AN:

1458534

Hom.:

Cov.:

AF XY:

0.0000579

AC XY:

AN XY:

725656

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33382

American (AMR)

AF:

0.00108

AC:

AN:

44260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26044

East Asian (EAS)

AF:

0.00

AC:

AN:

39642

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86156

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52510

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.0000549

AC:

AN:

1110632

Other (OTH)

AF:

0.0000665

AC:

AN:

60168

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

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:

0.0000656

AC:

AN:

152328

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41582

American (AMR)

AF:

0.000261

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

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:

0.0000573

Hom.:

Bravo

AF:

0.000102

ExAC

AF:

0.000132

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.46

CADD

Benign

4.0

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.090

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.54

M_CAP

Benign

0.0047

MetaRNN

Benign

0.016

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.95

PhyloP100

-0.41

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.070

REVEL

Benign

0.018

Sift

Benign

0.083

Sift4G

Benign

1.0

Polyphen

0.0020

Vest4

0.19

MVP

0.15

MPC

0.077

ClinPred

0.035

GERP RS

0.19

PromoterAI

-0.079

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.025

gMVP

0.38

Mutation Taster

=96/4

polymorphism

(source)

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

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