rs55658431
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_003640.5(ELP1):c.3014C>T(p.Ala1005Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,613,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. A1005A) has been classified as Likely benign.
Frequency
Consequence
NM_003640.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ELP1 | NM_003640.5 | c.3014C>T | p.Ala1005Val | missense_variant | 28/37 | ENST00000374647.10 | |
ELP1 | NM_001318360.2 | c.2672C>T | p.Ala891Val | missense_variant | 28/37 | ||
ELP1 | NM_001330749.2 | c.1967C>T | p.Ala656Val | missense_variant | 26/35 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ELP1 | ENST00000374647.10 | c.3014C>T | p.Ala1005Val | missense_variant | 28/37 | 1 | NM_003640.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152156Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250568Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135478
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461770Hom.: 0 Cov.: 34 AF XY: 0.0000110 AC XY: 8AN XY: 727178
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152156Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74342
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 07, 2016 | A variant of uncertain significance has been identified in the IKBKAP gene. The A1005V variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The A1005V variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A1005V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Alanine are tolerated across species. However, in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 10, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1005 of the ELP1 protein (p.Ala1005Val). This variant is present in population databases (rs55658431, gnomAD 0.005%). 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: 246548). 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 disruptive. 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. - |
Familial dysautonomia Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 24, 2020 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 06, 2023 | The c.3014C>T (p.A1005V) alteration is located in exon 28 (coding exon 27) of the IKBKAP gene. This alteration results from a C to T substitution at nucleotide position 3014, causing the alanine (A) at amino acid position 1005 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Familial dysautonomia;C0025149:Medulloblastoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 24, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at