Variant rs3003601 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_016035.5(COQ4):c.149G>A(p.Gly50Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G50A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 36)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

COQ4
NM_016035.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0510

Variant links:

Genes affected

COQ4 (HGNC:19693): (coenzyme Q4) This gene encodes a component of the coenzyme Q biosynthesis pathway. Coenzyme Q, an essential component of the electron transport chain, shuttles electrons between complexes I or II to complex III of the mitochondrial transport chain. This protein appears to play a structural role in stabilizing a complex that contains most of the coenzyme Q biosynthesis enzymes. Mutations in this gene are associated with mitochondrial disorders linked to coenzyme Q deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

COQ4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1

In a chain Ubiquinone biosynthesis protein COQ4 homolog, mitochondrial (size 234) in uniprot entity COQ4_HUMAN there are 27 pathogenic changes around while only 3 benign (90%) in NM_016035.5

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.108132124).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COQ4	NM_016035.5 linkuse as main transcript	c.149G>A	p.Gly50Glu	missense_variant	2/7	ENST00000300452.8	NP_057119.3	Q9Y3A0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
COQ4	ENST00000300452.8 linkuse as main transcript	c.149G>A	p.Gly50Glu	missense_variant	2/7	1	NM_016035.5	ENSP00000300452.3	Q9Y3A0-1
COQ4	ENST00000372875.3 linkuse as main transcript	c.149G>A	p.Gly50Glu	missense_variant	2/4	2		ENSP00000361966.3	Q5T4B9
COQ4	ENST00000608951.5 linkuse as main transcript	c.149G>A	p.Gly50Glu	missense_variant	2/3	2		ENSP00000476323.1	V9GY32
COQ4	ENST00000609948.1 linkuse as main transcript	c.149G>A	p.Gly50Glu	missense_variant	2/2	2		ENSP00000477292.1	V9GZ09

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1459538

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726160

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.60

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.21

T;D;.;.

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.64

T;T;T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;.;.;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.78

N;.;.;N

REVEL

Benign

0.046

Sift

Benign

0.052

T;.;.;T

Sift4G

Benign

0.43

T;T;T;D

Polyphen

0.049

B;.;.;P

Vest4

0.17

MutPred

0.65

Loss of catalytic residue at P46 (P = 0.0829);Loss of catalytic residue at P46 (P = 0.0829);Loss of catalytic residue at P46 (P = 0.0829);Loss of catalytic residue at P46 (P = 0.0829);

MVP

0.14

MPC

0.53

ClinPred

0.30

GERP RS

-2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.33

gMVP

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over