dbSNP rs757566504: COQ4:p.Leu4Met (chr9-128322868-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016035.5(COQ4):c.10C>A(p.Leu4Met) 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. L4Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

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: -0.250

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.077946186).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COQ4	NM_016035.5 link	c.10C>A	p.Leu4Met	missense_variant	Exon 1 of 7	ENST00000300452.8	NP_057119.3	Q9Y3A0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
COQ4	ENST00000300452.8 link	c.10C>A	p.Leu4Met	missense_variant	Exon 1 of 7	1	NM_016035.5	ENSP00000300452.3	Q9Y3A0-1
COQ4	ENST00000372875.3 link	c.10C>A	p.Leu4Met	missense_variant	Exon 1 of 4	2		ENSP00000361966.3	Q5T4B9
COQ4	ENST00000608951.5 link	c.10C>A	p.Leu4Met	missense_variant	Exon 1 of 3	2		ENSP00000476323.1	V9GY32
COQ4	ENST00000609948.1 link	c.10C>A	p.Leu4Met	missense_variant	Exon 1 of 2	2		ENSP00000477292.1	V9GZ09

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1421648

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

705110

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.:

Bravo

AF:

0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

7.6

DANN

Benign

0.73

DEOGEN2

Benign

0.0044

T;T;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.071

LIST_S2

Benign

0.40

T;T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.078

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

L;.;.;.

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.35

N;.;.;N

REVEL

Benign

0.069

Sift

Uncertain

0.018

D;.;.;D

Sift4G

Benign

0.072

T;T;D;T

Polyphen

0.44

B;.;.;P

Vest4

0.25

MVP

0.088

MPC

0.74

ClinPred

0.44

GERP RS

0.016

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.094

gMVP

0.51

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

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