11-31509914-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_019040.5(ELP4):​c.130C>A​(p.Pro44Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ELP4
NM_019040.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.108
Variant links:
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.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07625964).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ELP4NM_019040.5 linkc.130C>A p.Pro44Thr missense_variant Exon 1 of 10 ENST00000640961.2 NP_061913.3 Q96EB1-1
ELP4NM_001288726.2 linkc.130C>A p.Pro44Thr missense_variant Exon 1 of 12 NP_001275655.1 Q96EB1G5E9D4
ELP4NM_001288725.2 linkc.130C>A p.Pro44Thr missense_variant Exon 1 of 11 NP_001275654.1 Q96EB1-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ELP4ENST00000640961.2 linkc.130C>A p.Pro44Thr missense_variant Exon 1 of 10 1 NM_019040.5 ENSP00000492152.1 Q96EB1-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 10, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.130C>A (p.P44T) alteration is located in exon 1 (coding exon 1) of the ELP4 gene. This alteration results from a C to A substitution at nucleotide position 130, causing the proline (P) at amino acid position 44 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.073
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
16
DANN
Benign
0.97
DEOGEN2
Benign
0.0083
T;.;.;.;.;.;.;.;.;.;.;.;.
Eigen
Benign
-0.54
Eigen_PC
Benign
-0.41
FATHMM_MKL
Benign
0.43
N
LIST_S2
Benign
0.79
T;T;T;T;T;T;T;T;T;T;T;T;T
M_CAP
Benign
0.025
D
MetaRNN
Benign
0.076
T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.5
L;.;L;.;.;.;.;.;.;.;.;.;.
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-0.68
.;.;N;.;N;.;.;.;.;.;.;.;N
REVEL
Benign
0.026
Sift
Benign
0.041
.;.;D;.;T;.;.;.;.;.;.;.;T
Sift4G
Uncertain
0.034
.;.;D;.;T;.;.;.;.;.;.;.;D
Polyphen
0.0020
B;.;.;.;.;.;.;.;.;.;.;.;B
Vest4
0.11, 0.12, 0.099
MutPred
0.41
Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);
MVP
0.41
MPC
0.058
ClinPred
0.075
T
GERP RS
1.9
Varity_R
0.035
gMVP
0.38

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-31531461; API