11-31603795-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_019040.5(ELP4):c.541G>A(p.Gly181Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000497 in 1,608,232 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 (★).
Frequency
Consequence
NM_019040.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ELP4 | NM_019040.5 | c.541G>A | p.Gly181Ser | missense_variant | Exon 5 of 10 | ENST00000640961.2 | NP_061913.3 | |
ELP4 | NM_001288726.2 | c.541G>A | p.Gly181Ser | missense_variant | Exon 5 of 12 | NP_001275655.1 | ||
ELP4 | NM_001288725.2 | c.544G>A | p.Gly182Ser | missense_variant | Exon 5 of 11 | NP_001275654.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000660 AC: 1AN: 151582Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 247056Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134230
GnomAD4 exome AF: 0.00000481 AC: 7AN: 1456650Hom.: 0 Cov.: 30 AF XY: 0.00000690 AC XY: 5AN XY: 724672
GnomAD4 genome AF: 0.00000660 AC: 1AN: 151582Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74002
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 181 of the ELP4 protein (p.Gly181Ser). This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ELP4-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at