X-47142334-G-T
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_001135998.3(NDUFB11):c.445C>A(p.Leu149Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000166 in 1,207,606 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 22)
Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )
Consequence
NDUFB11
NM_001135998.3 missense
NM_001135998.3 missense
Scores
2
9
6
Clinical Significance
Conservation
PhyloP100: 2.14
Publications
0 publications found
Genes affected
NDUFB11 (HGNC:20372): (NADH:ubiquinone oxidoreductase subunit B11) The protein encoded by this gene is a subunit of the multisubunit NADH:ubiquinone oxidoreductase (complex I). Mammalian complex I is located at the mitochondrial inner membrane. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to ubiquinone. Mutations in the human gene are associated with linear skin defects with multiple congenital anomalies 3 and mitochondrial complex I deficiency. [provided by RefSeq, Dec 2016]
NDUFB11 Gene-Disease associations (from GenCC):
- mitochondrial diseaseInheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
- linear skin defects with multiple congenital anomalies 3Inheritance: XL Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
- mitochondrial complex I deficiency, nuclear type 30Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- linear skin defects with multiple congenital anomaliesInheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.00000895 AC: 1AN: 111733Hom.: 0 Cov.: 22 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
111733
Hom.:
Cov.:
22
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 9.13e-7 AC: 1AN: 1095873Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 361489 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1095873
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
361489
show subpopulations
African (AFR)
AF:
AC:
1
AN:
26369
American (AMR)
AF:
AC:
0
AN:
35018
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
19353
East Asian (EAS)
AF:
AC:
0
AN:
30176
South Asian (SAS)
AF:
AC:
0
AN:
53750
European-Finnish (FIN)
AF:
AC:
0
AN:
39777
Middle Eastern (MID)
AF:
AC:
0
AN:
4118
European-Non Finnish (NFE)
AF:
AC:
0
AN:
841267
Other (OTH)
AF:
AC:
0
AN:
46045
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000895 AC: 1AN: 111733Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33897 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
1
AN:
111733
Hom.:
Cov.:
22
AF XY:
AC XY:
0
AN XY:
33897
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
30715
American (AMR)
AF:
AC:
0
AN:
10485
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
2646
East Asian (EAS)
AF:
AC:
0
AN:
3564
South Asian (SAS)
AF:
AC:
0
AN:
2675
European-Finnish (FIN)
AF:
AC:
0
AN:
6082
Middle Eastern (MID)
AF:
AC:
0
AN:
236
European-Non Finnish (NFE)
AF:
AC:
0
AN:
53145
Other (OTH)
AF:
AC:
0
AN:
1500
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.325
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Jan 27, 2022
GeneDx
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
In silico analysis supports that this missense variant does not alter protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
T;.
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Uncertain
T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MVP
MPC
1.1
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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