Variant rs138560167 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.445G>A(p.Asp149Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. D149H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

COQ4
NM_016035.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.16

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 hotspot region, there are 4 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 1 benign, 3 uncertain in NM_016035.5

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25287497).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
COQ4	NM_016035.5 linkuse as main transcript	c.445G>A	p.Asp149Asn	missense_variant	5/7	ENST00000300452.8
COQ4	XM_047423449.1 linkuse as main transcript	c.*45G>A		3_prime_UTR_variant	4/4
COQ4	NM_001305942.2 linkuse as main transcript	c.*3-1279G>A		intron_variant
COQ4	XM_017014792.2 linkuse as main transcript	c.*3-655G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COQ4	ENST00000300452.8 linkuse as main transcript	c.445G>A	p.Asp149Asn	missense_variant	5/7	1	NM_016035.5	P1	Q9Y3A0-1
COQ4	ENST00000461102.1 linkuse as main transcript	n.1784G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000848

AC:

AN:

235792

Hom.:

AF XY:

0.0000157

AC XY:

AN XY:

127368

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000566

Gnomad SAS exome

AF:

0.0000350

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453406

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722156

show subpopulations

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:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.58

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.0016

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.017

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.9

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.13

Sift

Benign

0.055

Sift4G

Benign

0.090

Polyphen

0.12

Vest4

0.26

MutPred

0.71

Loss of disorder (P = 0.1725);

MVP

0.56

MPC

0.50

ClinPred

0.67

GERP RS

4.0

Varity_R

0.33

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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