11-31603795-G-A
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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
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
ELP4
NM_019040.5 missense
NM_019040.5 missense
Scores
8
5
6
Clinical Significance
Conservation
PhyloP100: 8.29
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 Likely_benign. Variant got -2 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.873
BS2
High AC in GnomAdExome4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ELP4 | NM_019040.5 | c.541G>A | p.Gly181Ser | missense_variant | 5/10 | ENST00000640961.2 | NP_061913.3 | |
ELP4 | NM_001288726.2 | c.541G>A | p.Gly181Ser | missense_variant | 5/12 | NP_001275655.1 | ||
ELP4 | NM_001288725.2 | c.544G>A | p.Gly182Ser | missense_variant | 5/11 | NP_001275654.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ELP4 | ENST00000640961.2 | c.541G>A | p.Gly181Ser | missense_variant | 5/10 | 1 | NM_019040.5 | ENSP00000492152 | P3 |
Frequencies
GnomAD3 genomes AF: 0.00000660 AC: 1AN: 151582Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000121 AC: 3AN: 247056Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134230
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GnomAD4 exome AF: 0.00000481 AC: 7AN: 1456650Hom.: 0 Cov.: 30 AF XY: 0.00000690 AC XY: 5AN XY: 724672
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GnomAD4 genome AF: 0.00000660 AC: 1AN: 151582Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74002
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 26, 2023 | 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
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
Benign
T
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.;.;.;.;.;.;.;.;.;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
.;.;D;.;.;.;.;.;.;.;.;D
REVEL
Uncertain
Sift
Benign
.;.;D;.;.;.;.;.;.;.;.;T
Sift4G
Uncertain
.;.;D;.;.;.;.;.;.;.;.;D
Polyphen
D;.;.;.;.;.;.;.;.;.;.;D
Vest4
0.81, 0.90
MutPred
Gain of phosphorylation at G181 (P = 0.0313);Gain of phosphorylation at G181 (P = 0.0313);.;Gain of phosphorylation at G181 (P = 0.0313);.;Gain of phosphorylation at G181 (P = 0.0313);.;Gain of phosphorylation at G181 (P = 0.0313);.;Gain of phosphorylation at G181 (P = 0.0313);Gain of phosphorylation at G181 (P = 0.0313);Gain of phosphorylation at G181 (P = 0.0313);
MVP
0.72
MPC
0.25
ClinPred
D
GERP RS
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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