rs143494120
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003640.5(ELP1):āc.154A>Gā(p.Lys52Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000471 in 1,613,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_003640.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ELP1 | NM_003640.5 | c.154A>G | p.Lys52Glu | missense_variant | 3/37 | ENST00000374647.10 | |
ELP1 | XM_047423991.1 | c.154A>G | p.Lys52Glu | missense_variant | 3/25 | ||
ELP1 | NM_001318360.2 | c.-189A>G | 5_prime_UTR_variant | 3/37 | |||
ELP1 | NM_001330749.2 | c.-706A>G | 5_prime_UTR_variant | 3/35 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ELP1 | ENST00000374647.10 | c.154A>G | p.Lys52Glu | missense_variant | 3/37 | 1 | NM_003640.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152228Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000995 AC: 25AN: 251320Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135876
GnomAD4 exome AF: 0.0000486 AC: 71AN: 1461226Hom.: 0 Cov.: 31 AF XY: 0.0000440 AC XY: 32AN XY: 726932
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74378
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 02, 2022 | The p.K52E variant (also known as c.154A>G), located in coding exon 2 of the IKBKAP gene, results from an A to G substitution at nucleotide position 154. The lysine at codon 52 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Familial dysautonomia Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jul 09, 2020 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 25, 2022 | This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 52 of the ELP1 protein (p.Lys52Glu). This variant is present in population databases (rs143494120, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ELP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 455955). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at