Variant 6-99376129-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_017421.4(COQ3):c.540C>T(p.Asn180Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00258 in 1,613,982 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 6 hom. )

Consequence

COQ3
NM_017421.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.49

Variant links:

Genes affected

COQ3 (HGNC:18175): (coenzyme Q3, methyltransferase) Ubiquinone, also known as coenzyme Q, or Q, is a critical component of the electron transport pathways of both eukaryotes and prokaryotes (Jonassen and Clarke, 2000 [PubMed 10777520]). This lipid consists of a hydrophobic isoprenoid tail and a quinone head group. The tail varies in length depending on the organism, but its purpose is to anchor coenzyme Q to the membrane. The quinone head group is responsible for the activity of coenzyme Q in the respiratory chain. The S. cerevisiae COQ3 gene encodes an O-methyltransferase required for 2 steps in the biosynthetic pathway of coenzyme Q. This enzyme methylates an early coenzyme Q intermediate, 3,4-dihydroxy-5-polyprenylbenzoic acid, as well as the final intermediate in the pathway, converting demethyl-ubiquinone to coenzyme Q. The COQ3 gene product is also capable of methylating the distinct prokaryotic early intermediate 2-hydroxy-6-polyprenyl phenol.[supplied by OMIM, Mar 2008]

COQ3 links:

COQ3 (HGNC:):

COQ3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 6-99376129-G-A is Benign according to our data. Variant chr6-99376129-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2656779.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.49 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COQ3	NM_017421.4 linkuse as main transcript	c.540C>T	p.Asn180Asn	synonymous_variant	5/7	ENST00000254759.8	NP_059117.3	Q9NZJ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
COQ3	ENST00000254759.8 linkuse as main transcript	c.540C>T	p.Asn180Asn	synonymous_variant	5/7	1	NM_017421.4	ENSP00000254759.3	Q9NZJ6
COQ3	ENST00000369240.5 linkuse as main transcript	c.45+1257C>T		intron_variant		5		ENSP00000358243.1	F6WGP0
COQ3	ENST00000479163.1 linkuse as main transcript	n.675C>T		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes

AF:

0.00266

AC:

405

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000773

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.00635

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00378

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00195

AC:

490

AN:

251310

Hom.:

AF XY:

0.00180

AC XY:

244

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00295

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000508

Gnomad NFE exome

AF:

0.00312

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00257

AC:

3760

AN:

1461788

Hom.:

Cov.:

AF XY:

0.00248

AC XY:

1807

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.00344

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.000656

Gnomad4 NFE exome

AF:

0.00308

Gnomad4 OTH exome

AF:

0.00202

GnomAD4 genome

AF:

0.00266

AC:

405

AN:

152194

Hom.:

Cov.:

AF XY:

0.00255

AC XY:

190

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.000771

Gnomad4 AMR

AF:

0.00634

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00378

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00267

Hom.:

Bravo

AF:

0.00308

EpiCase

AF:

0.00376

EpiControl

AF:

0.00249

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2022

COQ3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

8.3

DANN

Benign

0.65

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