chr11-31594876-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_StrongBS2
The NM_019040.5(ELP4):c.488G>A(p.Arg163His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000429 in 1,560,200 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
Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000035 ( 0 hom. )
Consequence
ELP4
NM_019040.5 missense
NM_019040.5 missense
Scores
13
4
2
Clinical Significance
Conservation
PhyloP100: 8.48
Genes affected
ELP4 (HGNC:1171): (elongator acetyltransferase complex subunit 4) This gene encodes a component of the six subunit elongator complex, a histone acetyltransferase complex that associates directly with RNA polymerase II during transcriptional elongation. The human gene can partially complement sensitivity phenotypes of yeast ELP4 deletion mutants. This gene has also been associated with Rolandic epilepsy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.963
BS2
High AC in GnomAd4 at 18 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ELP4 | NM_019040.5 | c.488G>A | p.Arg163His | missense_variant | 4/10 | ENST00000640961.2 | NP_061913.3 | |
ELP4 | NM_001288726.2 | c.488G>A | p.Arg163His | missense_variant | 4/12 | NP_001275655.1 | ||
ELP4 | NM_001288725.2 | c.488G>A | p.Arg163His | missense_variant | 4/11 | NP_001275654.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ELP4 | ENST00000640961.2 | c.488G>A | p.Arg163His | missense_variant | 4/10 | 1 | NM_019040.5 | ENSP00000492152 | P3 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152032Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000246 AC: 5AN: 202904Hom.: 0 AF XY: 0.0000269 AC XY: 3AN XY: 111424
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GnomAD4 exome AF: 0.0000348 AC: 49AN: 1408050Hom.: 0 Cov.: 29 AF XY: 0.0000358 AC XY: 25AN XY: 698874
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GnomAD4 genome AF: 0.000118 AC: 18AN: 152150Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10AN XY: 74380
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 28, 2023 | The c.488G>A (p.R163H) alteration is located in exon 4 (coding exon 4) of the ELP4 gene. This alteration results from a G to A substitution at nucleotide position 488, causing the arginine (R) at amino acid position 163 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 27, 2023 | 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. ClinVar contains an entry for this variant (Variation ID: 2517420). This variant has not been reported in the literature in individuals affected with ELP4-related conditions. 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 sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 163 of the ELP4 protein (p.Arg163His). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;.;.;.;.;.;.;.;.;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;.;H;.;.;.;.;.;.;.;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
.;.;D;.;D;.;.;.;.;.;.;D
REVEL
Pathogenic
Sift
Pathogenic
.;.;D;.;D;.;.;.;.;.;.;D
Sift4G
Uncertain
.;.;D;.;D;.;.;.;.;.;.;D
Polyphen
D;.;.;.;.;.;.;.;.;.;.;D
Vest4
0.86, 0.94, 0.93
MutPred
Loss of MoRF binding (P = 0.0172);Loss of MoRF binding (P = 0.0172);Loss of MoRF binding (P = 0.0172);Loss of MoRF binding (P = 0.0172);Loss of MoRF binding (P = 0.0172);Loss of MoRF binding (P = 0.0172);Loss of MoRF binding (P = 0.0172);Loss of MoRF binding (P = 0.0172);Loss of MoRF binding (P = 0.0172);Loss of MoRF binding (P = 0.0172);Loss of MoRF binding (P = 0.0172);Loss of MoRF binding (P = 0.0172);
MVP
0.77
MPC
0.37
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at