11-62672058-T-G

Position:

chr11-62672058-T-G

Variant summary

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

The NM_001085372.3(UQCC3):c.226T>G(p.Trp76Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,609,326 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0072 ( 13 hom., cov: 32)

Exomes 𝑓: 0.00074 ( 11 hom. )

Consequence

UQCC3
NM_001085372.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.611

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008778036).

BP6

Variant 11-62672058-T-G is Benign according to our data. Variant chr11-62672058-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 376907.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00716 (1090/152302) while in subpopulation AFR AF= 0.0254 (1056/41570). AF 95% confidence interval is 0.0241. There are 13 homozygotes in gnomad4. There are 527 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UQCC3	NM_001085372.3 linkuse as main transcript	c.226T>G	p.Trp76Gly	missense_variant	2/2	ENST00000377953.4	NP_001078841.1	Q6UW78
LBHD1	NM_024099.5 linkuse as main transcript	c.-505A>C		5_prime_UTR_variant	1/7	ENST00000354588.8	NP_077004.2	Q9BQE6-2A0A024R584

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
UQCC3	ENST00000377953.4 linkuse as main transcript	c.226T>G	p.Trp76Gly	missense_variant	2/2	1	NM_001085372.3	ENSP00000367189.3	Q6UW78
LBHD1	ENST00000354588.8 linkuse as main transcript	c.-505A>C		5_prime_UTR_variant	1/7	1	NM_024099.5	ENSP00000346600.3	Q9BQE6-2
UQCC3	ENST00000531323.1 linkuse as main transcript	c.226T>G	p.Trp76Gly	missense_variant	3/3	3		ENSP00000432692.1	Q6UW78
LBHD1	ENST00000528862.2 linkuse as main transcript	c.93+69A>C		intron_variant		3		ENSP00000434489.2	E9PQ29

Frequencies

GnomAD3 genomes

AF:

0.00715

AC:

1088

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0254

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

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:

0.000132

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00162

AC:

381

AN:

234640

Hom.:

AF XY:

0.00118

AC XY:

151

AN XY:

127962

show subpopulations

Gnomad AFR exome

AF:

0.0248

Gnomad AMR exome

AF:

0.000638

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000567

Gnomad OTH exome

AF:

0.000869

GnomAD4 exome

AF:

0.000738

AC:

1075

AN:

1457024

Hom.:

Cov.:

AF XY:

0.000560

AC XY:

406

AN XY:

724416

show subpopulations

Gnomad4 AFR exome

AF:

0.0273

Gnomad4 AMR exome

AF:

0.000801

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000468

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000261

Gnomad4 OTH exome

AF:

0.00145

GnomAD4 genome

AF:

0.00716

AC:

1090

AN:

152302

Hom.:

Cov.:

AF XY:

0.00708

AC XY:

527

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0254

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00129

Hom.:

Bravo

AF:

0.00786

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0219

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.00197

AC:

239

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Dec 30, 2016	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 12, 2023	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 15, 2017

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.65

DEOGEN2

Uncertain

0.65

D;D

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.57

.;T

MetaRNN

Benign

0.0088

T;T

MetaSVM

Benign

-0.95

PROVEAN

Pathogenic

-4.4

D;D

REVEL

Benign

0.083

Sift

Benign

0.11

T;T

Sift4G

Uncertain

0.051

T;T

Polyphen

0.84

P;P

Vest4

0.49

MVP

0.19

MPC

1.1

ClinPred

0.055

GERP RS

0.086

Varity_R

0.28

gMVP

0.094

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