11-31594882-A-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_019040.5(ELP4):āc.494A>Cā(p.Gln165Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,407,920 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 (ā ).
Frequency
Genomes: not found (cov: 33)
Exomes š: 7.1e-7 ( 0 hom. )
Consequence
ELP4
NM_019040.5 missense
NM_019040.5 missense
Scores
10
5
4
Clinical Significance
Conservation
PhyloP100: 7.91
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 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.883
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ELP4 | NM_019040.5 | c.494A>C | p.Gln165Pro | missense_variant | 4/10 | ENST00000640961.2 | NP_061913.3 | |
ELP4 | NM_001288726.2 | c.494A>C | p.Gln165Pro | missense_variant | 4/12 | NP_001275655.1 | ||
ELP4 | NM_001288725.2 | c.494A>C | p.Gln165Pro | missense_variant | 4/11 | NP_001275654.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ELP4 | ENST00000640961.2 | c.494A>C | p.Gln165Pro | missense_variant | 4/10 | 1 | NM_019040.5 | ENSP00000492152 | P3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 7.10e-7 AC: 1AN: 1407920Hom.: 0 Cov.: 30 AF XY: 0.00000143 AC XY: 1AN XY: 698832
GnomAD4 exome
AF:
AC:
1
AN:
1407920
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Cov.:
30
AF XY:
AC XY:
1
AN XY:
698832
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
Bravo
AF:
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 | Dec 14, 2023 | This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 165 of the ELP4 protein (p.Gln165Pro). This variant is not present in population databases (gnomAD no frequency). 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
Pathogenic
BayesDel_addAF
Pathogenic
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
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.;M;.;.;.;.;.;.;.;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
.;.;D;.;D;.;.;.;.;.;.;D
REVEL
Uncertain
Sift
Uncertain
.;.;D;.;D;.;.;.;.;.;.;D
Sift4G
Uncertain
.;.;D;.;D;.;.;.;.;.;.;D
Polyphen
D;.;.;.;.;.;.;.;.;.;.;D
Vest4
0.76, 0.78, 0.80
MutPred
Loss of MoRF binding (P = 0.0542);Loss of MoRF binding (P = 0.0542);Loss of MoRF binding (P = 0.0542);Loss of MoRF binding (P = 0.0542);Loss of MoRF binding (P = 0.0542);Loss of MoRF binding (P = 0.0542);Loss of MoRF binding (P = 0.0542);Loss of MoRF binding (P = 0.0542);Loss of MoRF binding (P = 0.0542);Loss of MoRF binding (P = 0.0542);Loss of MoRF binding (P = 0.0542);Loss of MoRF binding (P = 0.0542);
MVP
0.78
MPC
0.37
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at