Variant rs375750495 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_016035.5(COQ4):c.48G>C(p.Pro16=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000198 in 1,596,868 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

COQ4
NM_016035.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.29

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 Benign. Variant got -11 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 9-128322906-G-C is Benign according to our data. Variant chr9-128322906-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 476184.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.29 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COQ4	NM_016035.5 linkuse as main transcript	c.48G>C	p.Pro16=	synonymous_variant	1/7	ENST00000300452.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COQ4	ENST00000300452.8 linkuse as main transcript	c.48G>C	p.Pro16=	synonymous_variant	1/7	1	NM_016035.5	P1	Q9Y3A0-1
COQ4	ENST00000372875.3 linkuse as main transcript	c.48G>C	p.Pro16=	synonymous_variant	1/4	2
COQ4	ENST00000608951.5 linkuse as main transcript	c.48G>C	p.Pro16=	synonymous_variant	1/3	2
COQ4	ENST00000609948.1 linkuse as main transcript	c.48G>C	p.Pro16=	synonymous_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.00107

AC:

163

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00367

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000198

AC:

AN:

212268

Hom.:

AF XY:

0.000152

AC XY:

AN XY:

118554

show subpopulations

Gnomad AFR exome

AF:

0.00266

Gnomad AMR exome

AF:

0.000244

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000342

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000108

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000104

AC:

150

AN:

1444534

Hom.:

Cov.:

AF XY:

0.0000905

AC XY:

AN XY:

718404

show subpopulations

Gnomad4 AFR exome

AF:

0.00356

Gnomad4 AMR exome

AF:

0.000253

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.03e-7

Gnomad4 OTH exome

AF:

0.000284

GnomAD4 genome

AF:

0.00109

AC:

166

AN:

152334

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00373

Gnomad4 AMR

AF:

0.000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000315

Hom.:

Bravo

AF:

0.00133

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 04, 2024

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 23, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

Cadd

Benign

0.49

Dann

Benign

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over