Variant 9-128322834-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000608951(COQ4):c.-25C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0032 in 1,528,794 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0045 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0031 ( 87 hom. )

Consequence

COQ4
ENST00000608951 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.00700

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 9-128322834-C-T is Benign according to our data. Variant chr9-128322834-C-T is described in ClinVar as [Benign]. Clinvar id is 381170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00448 (682/152384) while in subpopulation SAS AF= 0.0352 (170/4832). AF 95% confidence interval is 0.0309. There are 7 homozygotes in gnomad4. There are 377 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COQ4	NM_016035.5 link	c.-25C>T		upstream_gene_variant		ENST00000300452.8	NP_057119.3	Q9Y3A0-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COQ4	ENST00000608951 link	c.-25C>T	5_prime_UTR_variant	Exon 1 of 3	2		ENSP00000476323.1	V9GY32
COQ4	ENST00000609948 link	c.-25C>T	5_prime_UTR_variant	Exon 1 of 2	2		ENSP00000477292.1	V9GZ09
COQ4	ENST00000300452.8 link	c.-25C>T	upstream_gene_variant		1	NM_016035.5	ENSP00000300452.3	Q9Y3A0-1
COQ4	ENST00000372875.3 link	c.-25C>T	upstream_gene_variant		2		ENSP00000361966.3	Q5T4B9

Frequencies

GnomAD3 genomes

AF:

0.00451

AC:

686

AN:

152266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00817

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00471

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0354

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00116

Gnomad OTH

AF:

0.00764

GnomAD3 exomes

AF:

0.00763

AC:

1018

AN:

133402

Hom.:

AF XY:

0.00916

AC XY:

672

AN XY:

73346

show subpopulations

Gnomad AFR exome

AF:

0.00927

Gnomad AMR exome

AF:

0.00565

Gnomad ASJ exome

AF:

0.000276

Gnomad EAS exome

AF:

0.000198

Gnomad SAS exome

AF:

0.0343

Gnomad FIN exome

AF:

0.000214

Gnomad NFE exome

AF:

0.000855

Gnomad OTH exome

AF:

0.00843

GnomAD4 exome

AF:

0.00306

AC:

4208

AN:

1376410

Hom.:

Cov.:

AF XY:

0.00400

AC XY:

2712

AN XY:

678726

show subpopulations

Gnomad4 AFR exome

AF:

0.00936

Gnomad4 AMR exome

AF:

0.00564

Gnomad4 ASJ exome

AF:

0.000495

Gnomad4 EAS exome

AF:

0.0000846

Gnomad4 SAS exome

AF:

0.0326

Gnomad4 FIN exome

AF:

0.000223

Gnomad4 NFE exome

AF:

0.000772

Gnomad4 OTH exome

AF:

0.00523

GnomAD4 genome

AF:

0.00448

AC:

682

AN:

152384

Hom.:

Cov.:

AF XY:

0.00506

AC XY:

377

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.00808

Gnomad4 AMR

AF:

0.00470

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0352

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00116

Gnomad4 OTH

AF:

0.00756

Alfa

AF:

0.00269

Hom.:

Bravo

AF:

0.00430

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Jun 30, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

9.3

DANN

Benign

0.87

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