chr11-31603802-A-G
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_019040.5(ELP4):c.548A>G(p.Tyr183Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000106 in 1,611,042 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: 0.000011 ( 0 hom. )
Consequence
ELP4
NM_019040.5 missense
NM_019040.5 missense
Scores
6
8
5
Clinical Significance
Conservation
PhyloP100: 5.99
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 -3 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.782
BS2
High AC in GnomAdExome4 at 16 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ELP4 | NM_019040.5 | c.548A>G | p.Tyr183Cys | missense_variant | 5/10 | ENST00000640961.2 | NP_061913.3 | |
ELP4 | NM_001288726.2 | c.548A>G | p.Tyr183Cys | missense_variant | 5/12 | NP_001275655.1 | ||
ELP4 | NM_001288725.2 | c.551A>G | p.Tyr184Cys | missense_variant | 5/11 | NP_001275654.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ELP4 | ENST00000640961.2 | c.548A>G | p.Tyr183Cys | missense_variant | 5/10 | 1 | NM_019040.5 | ENSP00000492152 | P3 |
Frequencies
GnomAD3 genomes AF: 0.00000659 AC: 1AN: 151814Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248494Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 134902
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GnomAD4 exome AF: 0.0000110 AC: 16AN: 1459228Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8AN XY: 726006
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GnomAD4 genome AF: 0.00000659 AC: 1AN: 151814Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74126
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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 | Apr 10, 2023 | 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. 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 tolerated. This variant has not been reported in the literature in individuals affected with ELP4-related conditions. This variant is present in population databases (rs771600237, gnomAD 0.0009%). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 183 of the ELP4 protein (p.Tyr183Cys). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.;.;.;.;.;.;.;.;.
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
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;.;.;.;.;.;.;D
REVEL
Uncertain
Sift
Uncertain
.;.;D;.;D;.;.;.;.;.;.;T
Sift4G
Uncertain
.;.;D;.;.;.;.;.;.;.;.;D
Polyphen
D;.;.;.;.;.;.;.;.;.;.;D
Vest4
0.80, 0.57
MutPred
Loss of phosphorylation at Y183 (P = 0.011);Loss of phosphorylation at Y183 (P = 0.011);.;Loss of phosphorylation at Y183 (P = 0.011);.;Loss of phosphorylation at Y183 (P = 0.011);.;Loss of phosphorylation at Y183 (P = 0.011);.;Loss of phosphorylation at Y183 (P = 0.011);Loss of phosphorylation at Y183 (P = 0.011);Loss of phosphorylation at Y183 (P = 0.011);
MVP
0.71
MPC
0.11
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