8-96231832-A-T

Position:

chr8-96231832-A-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_006294.5(UQCRB):c.200T>A(p.Leu67Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000828 in 1,614,178 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00070 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00084 ( 13 hom. )

Consequence

UQCRB
NM_006294.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: 8.98

Variant links:

Genes affected

UQCRB (HGNC:12582): (ubiquinol-cytochrome c reductase binding protein) This gene encodes a subunit of the ubiquinol-cytochrome c oxidoreductase complex, which consists of one mitochondrial-encoded and 10 nuclear-encoded subunits. The protein encoded by this gene binds ubiquinone and participates in the transfer of electrons when ubiquinone is bound. This protein plays an important role in hypoxia-induced angiogenesis through mitochondrial reactive oxygen species-mediated signaling. Mutations in this gene are associated with mitochondrial complex III deficiency. Alternatively spliced transcript variants have been found for this gene. Related pseudogenes have been identified on chromosomes 1, 5 and X. [provided by RefSeq, Dec 2011]

UQCRB links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06909698).

BP6

Variant 8-96231832-A-T is Benign according to our data. Variant chr8-96231832-A-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 288054.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Benign=1, Uncertain_significance=1}.

BS2

High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UQCRB	NM_006294.5 linkuse as main transcript	c.200T>A	p.Leu67Gln	missense_variant	3/4	ENST00000287022.10
UQCRB	NM_001254752.2 linkuse as main transcript	c.200T>A	p.Leu67Gln	missense_variant	3/5
UQCRB	NM_001199975.3 linkuse as main transcript	c.104T>A	p.Leu35Gln	missense_variant	4/5
UQCRB	NR_045639.2 linkuse as main transcript	n.215T>A		non_coding_transcript_exon_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UQCRB	ENST00000287022.10 linkuse as main transcript	c.200T>A	p.Leu67Gln	missense_variant	3/4	1	NM_006294.5	P1	P14927-1

Frequencies

GnomAD3 genomes

AF:

0.000703

AC:

107

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000735

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00127

AC:

320

AN:

251424

Hom.:

AF XY:

0.00163

AC XY:

221

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000694

Gnomad ASJ exome

AF:

0.00198

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00575

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000730

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.000841

AC:

1230

AN:

1461840

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

780

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000581

Gnomad4 ASJ exome

AF:

0.00191

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00594

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.000496

Gnomad4 OTH exome

AF:

0.000894

GnomAD4 genome

AF:

0.000702

AC:

107

AN:

152338

Hom.:

Cov.:

AF XY:

0.000913

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00104

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000735

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000938

Hom.:

Bravo

AF:

0.000688

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.00130

AC:

158

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00164

EpiControl

AF:

0.00196

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2022	UQCRB: BS2 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 27, 2019	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 08, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 02, 2024	- -

UQCRB-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 19, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Benign

-0.040

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

T;.;.;T

Eigen

Pathogenic

0.74

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.86

D;D;T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.069

T;T;T;T

MetaSVM

Benign

-0.33

MutationAssessor

Pathogenic

3.1

M;.;M;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-4.2

D;D;D;D

REVEL

Uncertain

0.57

Sift

Uncertain

0.012

D;D;D;D

Sift4G

Benign

0.11

T;D;D;D

Polyphen

1.0

D;.;.;.

Vest4

0.91

MVP

0.55

MPC

0.33

ClinPred

0.35

GERP RS

5.3

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.82

gMVP

0.71

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