11-62671858-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001085372.3(UQCC3):​c.113T>C​(p.Met38Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,613,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

UQCC3
NM_001085372.3 missense

Scores

2
10
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.37
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.114892155).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UQCC3NM_001085372.3 linkc.113T>C p.Met38Thr missense_variant Exon 1 of 2 ENST00000377953.4 NP_001078841.1 Q6UW78
LBHD1NM_024099.5 linkc.-305A>G 5_prime_UTR_variant Exon 1 of 7 ENST00000354588.8 NP_077004.2 Q9BQE6-2A0A024R584

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UQCC3ENST00000377953.4 linkc.113T>C p.Met38Thr missense_variant Exon 1 of 2 1 NM_001085372.3 ENSP00000367189.3 Q6UW78
LBHD1ENST00000354588.8 linkc.-305A>G 5_prime_UTR_variant Exon 1 of 7 1 NM_024099.5 ENSP00000346600.3 Q9BQE6-2
UQCC3ENST00000531323.1 linkc.113T>C p.Met38Thr missense_variant Exon 2 of 3 3 ENSP00000432692.1 Q6UW78
LBHD1ENST00000528862.2 linkc.93+269A>G intron_variant Intron 1 of 2 3 ENSP00000434489.2 E9PQ29

Frequencies

GnomAD3 genomes
AF:
0.000191
AC:
29
AN:
151958
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000701
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000602
AC:
15
AN:
249030
Hom.:
0
AF XY:
0.0000296
AC XY:
4
AN XY:
135248
show subpopulations
Gnomad AFR exome
AF:
0.000843
Gnomad AMR exome
AF:
0.0000580
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000116
AC:
17
AN:
1461796
Hom.:
0
Cov.:
31
AF XY:
0.00000825
AC XY:
6
AN XY:
727204
show subpopulations
Gnomad4 AFR exome
AF:
0.000358
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.000191
AC:
29
AN:
152076
Hom.:
0
Cov.:
33
AF XY:
0.000108
AC XY:
8
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.000699
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000124
Hom.:
0
Bravo
AF:
0.000230
ESP6500AA
AF:
0.000244
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000496
AC:
6

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Jan 12, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 38 of the UQCC3 protein (p.Met38Thr). This variant is present in population databases (rs376452919, gnomAD 0.08%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with UQCC3-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.65
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Uncertain
-0.080
CADD
Benign
22
DANN
Benign
0.97
DEOGEN2
Uncertain
0.66
D;D
Eigen
Uncertain
0.35
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Benign
0.47
.;T
M_CAP
Uncertain
0.12
D
MetaRNN
Benign
0.11
T;T
MetaSVM
Uncertain
-0.27
T
PROVEAN
Pathogenic
-4.9
D;D
REVEL
Uncertain
0.59
Sift
Uncertain
0.0030
D;D
Sift4G
Uncertain
0.0080
D;D
Polyphen
0.99
D;D
Vest4
0.43
MVP
0.28
MPC
0.48
ClinPred
0.57
D
GERP RS
5.0
Varity_R
0.70
gMVP
0.31

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs376452919; hg19: chr11-62439330; COSMIC: COSV99583361; COSMIC: COSV99583361; API