rs754821950
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_001136472.2(LITAF):c.418G>C(p.Ala140Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A140T) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 32)
Consequence
LITAF
NM_001136472.2 missense
NM_001136472.2 missense
Scores
3
11
5
Clinical Significance
Conservation
PhyloP100: 2.75
Genes affected
LITAF (HGNC:16841): (lipopolysaccharide induced TNF factor) Lipopolysaccharide is a potent stimulator of monocytes and macrophages, causing secretion of tumor necrosis factor-alpha (TNF-alpha) and other inflammatory mediators. This gene encodes lipopolysaccharide-induced TNF-alpha factor, which is a DNA-binding protein and can mediate the TNF-alpha expression by direct binding to the promoter region of the TNF-alpha gene. The transcription of this gene is induced by tumor suppressor p53 and has been implicated in the p53-induced apoptotic pathway. Mutations in this gene cause Charcot-Marie-Tooth disease type 1C (CMT1C) and may be involved in the carcinogenesis of extramammary Paget's disease (EMPD). Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM1
In a domain LITAF (size 84) in uniprot entity LITAF_HUMAN there are 18 pathogenic changes around while only 6 benign (75%) in NM_001136472.2
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Charcot-Marie-Tooth disease Uncertain:1
Aug 14, 2019
Genesis Genome Database
Significance: Uncertain significance
Review Status: no assertion criteria provided
Collection Method: research
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;D;D;D;.;D;D;D
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D;.;.;D;.;.;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Benign
M;M;M;M;.;M;M;.
PrimateAI
Uncertain
T
PROVEAN
Uncertain
.;.;N;.;.;.;.;.
REVEL
Pathogenic
Sift
Benign
.;.;D;.;.;.;.;.
Sift4G
Benign
T;T;T;T;T;T;T;.
Polyphen
D;D;D;D;.;D;D;.
Vest4
MutPred
Gain of loop (P = 0.0851);Gain of loop (P = 0.0851);Gain of loop (P = 0.0851);Gain of loop (P = 0.0851);.;Gain of loop (P = 0.0851);Gain of loop (P = 0.0851);Gain of loop (P = 0.0851);
MVP
MPC
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