rs201440191
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003640.5(ELP1):c.2845C>T(p.His949Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,613,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. H949H) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ELP1 | NM_003640.5 | c.2845C>T | p.His949Tyr | missense_variant | 26/37 | ENST00000374647.10 | |
ELP1 | NM_001318360.2 | c.2503C>T | p.His835Tyr | missense_variant | 26/37 | ||
ELP1 | NM_001330749.2 | c.1798C>T | p.His600Tyr | missense_variant | 24/35 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ELP1 | ENST00000374647.10 | c.2845C>T | p.His949Tyr | missense_variant | 26/37 | 1 | NM_003640.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152124Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000211 AC: 53AN: 251172Hom.: 0 AF XY: 0.000228 AC XY: 31AN XY: 135736
GnomAD4 exome AF: 0.0000383 AC: 56AN: 1461454Hom.: 0 Cov.: 30 AF XY: 0.0000440 AC XY: 32AN XY: 727036
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152242Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74444
ClinVar
Submissions by phenotype
Familial dysautonomia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Dec 30, 2019 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Familial dysautonomia;C0025149:Medulloblastoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 18, 2022 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 21, 2021 | This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 949 of the ELP1 protein (p.His949Tyr). This variant is present in population databases (rs201440191, gnomAD 0.2%). 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: 577389). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at