rs1438338245
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001199138.2(NLRC4):c.3052G>A(p.Ala1018Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000997 in 1,605,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1018G) has been classified as Uncertain significance.
Frequency
Consequence
NM_001199138.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NLRC4 | NM_001199138.2 | c.3052G>A | p.Ala1018Thr | missense_variant | 9/9 | ENST00000402280.6 | |
NLRC4 | NM_001199139.1 | c.3052G>A | p.Ala1018Thr | missense_variant | 9/9 | ||
NLRC4 | NM_021209.4 | c.3052G>A | p.Ala1018Thr | missense_variant | 9/9 | ||
NLRC4 | NM_001302504.1 | c.1057G>A | p.Ala353Thr | missense_variant | 8/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NLRC4 | ENST00000402280.6 | c.3052G>A | p.Ala1018Thr | missense_variant | 9/9 | 1 | NM_001199138.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152072Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000816 AC: 2AN: 245202Hom.: 0 AF XY: 0.00000753 AC XY: 1AN XY: 132722
GnomAD4 exome AF: 0.00000963 AC: 14AN: 1453288Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 10AN XY: 722546
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152072Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74274
ClinVar
Submissions by phenotype
Periodic fever-infantile enterocolitis-autoinflammatory syndrome;C4015276:Familial cold autoinflammatory syndrome 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2017 | This sequence change replaces alanine with threonine at codon 1018 of the NLRC4 protein (p.Ala1018Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NLRC4-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at