rs368999377
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_003640.5(ELP1):c.3032G>A(p.Arg1011His) variant causes a missense change. The variant allele was found at a frequency of 0.0000421 in 1,614,134 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R1011C) has been classified as Uncertain significance.
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.3032G>A | p.Arg1011His | missense_variant | 28/37 | ENST00000374647.10 | |
ELP1 | NM_001318360.2 | c.2690G>A | p.Arg897His | missense_variant | 28/37 | ||
ELP1 | NM_001330749.2 | c.1985G>A | p.Arg662His | missense_variant | 26/35 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ELP1 | ENST00000374647.10 | c.3032G>A | p.Arg1011His | missense_variant | 28/37 | 1 | NM_003640.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152170Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000638 AC: 16AN: 250766Hom.: 0 AF XY: 0.0000664 AC XY: 9AN XY: 135544
GnomAD4 exome AF: 0.0000417 AC: 61AN: 1461846Hom.: 0 Cov.: 34 AF XY: 0.0000426 AC XY: 31AN XY: 727214
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152288Hom.: 0 Cov.: 33 AF XY: 0.0000806 AC XY: 6AN XY: 74458
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 16, 2022 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1011 of the IKBKAP protein (p.Arg1011His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with IKBKAP-related conditions. ClinVar contains an entry for this variant (Variation ID: 526186). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. | Sep 16, 2020 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 27, 2023 | The c.3032G>A (p.R1011H) alteration is located in exon 28 (coding exon 27) of the IKBKAP gene. This alteration results from a G to A substitution at nucleotide position 3032, causing the arginine (R) at amino acid position 1011 to be replaced by a histidine (H). 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 | Oct 14, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at