11-62672038-C-T

Position:

chr11-62672038-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000377953.4(UQCC3):c.206C>T(p.Thr69Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000457 in 1,612,458 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00042 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00046 ( 3 hom. )

Consequence

UQCC3
ENST00000377953.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.36

Variant links:

Genes affected

UQCC3 (HGNC:34399): (ubiquinol-cytochrome c reductase complex assembly factor 3) Complex III is a mitochondrial inner membrane protein complex that transfers electrons from ubiquinol to cytochrome c. This gene encodes a protein that functions in complex III assembly. Mutations in this gene result in Mitochondrial complex III deficiency, nuclear type 9. [provided by RefSeq, Dec 2014]

UQCC3 links:

LBHD1 (HGNC:28351): (LBH domain containing 1) This gene shares three exons in common with another gene, chromosome 11 open reading frame 98 (GeneID:102288414), but the encoded protein uses a reading frame that is different from that of the chromosome 11 open reading frame 98 gene. [provided by RefSeq, Nov 2017]

LBHD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00707376).

BP6

Variant 11-62672038-C-T is Benign according to our data. Variant chr11-62672038-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 781960.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UQCC3	NM_001085372.3 linkuse as main transcript	c.206C>T	p.Thr69Ile	missense_variant	2/2	ENST00000377953.4	NP_001078841.1
LBHD1	NM_024099.5 linkuse as main transcript	c.-485G>A		5_prime_UTR_variant	1/7	ENST00000354588.8	NP_077004.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UQCC3	ENST00000377953.4 linkuse as main transcript	c.206C>T	p.Thr69Ile	missense_variant	2/2	1	NM_001085372.3	ENSP00000367189	P1
LBHD1	ENST00000354588.8 linkuse as main transcript	c.-485G>A		5_prime_UTR_variant	1/7	1	NM_024099.5	ENSP00000346600	P1	Q9BQE6-2
UQCC3	ENST00000531323.1 linkuse as main transcript	c.206C>T	p.Thr69Ile	missense_variant	3/3	3		ENSP00000432692	P1
LBHD1	ENST00000528862.2 linkuse as main transcript	c.93+89G>A		intron_variant		3		ENSP00000434489

Frequencies

GnomAD3 genomes

AF:

0.000420

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000788

AC:

191

AN:

242486

Hom.:

AF XY:

0.000886

AC XY:

117

AN XY:

132116

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000118

Gnomad ASJ exome

AF:

0.00822

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00179

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000428

Gnomad OTH exome

AF:

0.000847

GnomAD4 exome

AF:

0.000461

AC:

673

AN:

1460114

Hom.:

Cov.:

AF XY:

0.000516

AC XY:

375

AN XY:

726256

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000113

Gnomad4 ASJ exome

AF:

0.00788

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00171

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000214

Gnomad4 OTH exome

AF:

0.00104

GnomAD4 genome

AF:

0.000420

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.000483

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000735

Hom.:

Bravo

AF:

0.000419

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.000734

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 04, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

T;T

Eigen

Benign

0.0095

Eigen_PC

Benign

0.072

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.64

.;T

M_CAP

Benign

0.0053

MetaRNN

Benign

0.0071

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.98

N;N

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.043

Sift

Benign

0.059

T;T

Sift4G

Benign

0.11

T;T

Polyphen

0.36

B;B

Vest4

0.089

MVP

0.23

MPC

0.93

ClinPred

0.090

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

gMVP

0.038

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