11-31603790-G-T

Position:

• chr11-31603790-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_019040.5(ELP4):​c.536G>T​(p.Arg179Ile) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ELP4 NM_019040.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 2.96

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3217911).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELP4	NM_019040.5	c.536G>T	p.Arg179Ile	missense_variant	5/10	ENST00000640961.2
ELP4	NM_001288726.2	c.536G>T	p.Arg179Ile	missense_variant	5/12
ELP4	NM_001288725.2	c.539G>T	p.Arg180Ile	missense_variant	5/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELP4	ENST00000640961.2	c.536G>T	p.Arg179Ile	missense_variant	5/10	1	NM_019040.5	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

ELP4-related disorder Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 17, 2024

The ELP4 c.536G>T variant is predicted to result in the amino acid substitution p.Arg179Ile. To our knowledge, this variant has not been reported in the literature or in gnomAD, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.028	T;.;.;.;.;.;.;.;.;.;.;.
Eigen	Benign	-0.017
Eigen_PC	Benign	0.079
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.93	D;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.32	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M;.;.;.;.;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.2	.;.;D;.;.;.;.;.;.;.;.;D
REVEL	Benign	0.10
Sift	Benign	0.094	.;.;T;.;.;.;.;.;.;.;.;D
Sift4G	Benign	0.089	.;.;T;.;.;.;.;.;.;.;.;T
Polyphen		0.44	B;.;.;.;.;.;.;.;.;.;.;P
Vest4		0.36, 0.35
MutPred		0.70		Loss of disorder (P = 0.0393);Loss of disorder (P = 0.0393);.;Loss of disorder (P = 0.0393);.;Loss of disorder (P = 0.0393);.;Loss of disorder (P = 0.0393);.;Loss of disorder (P = 0.0393);Loss of disorder (P = 0.0393);Loss of disorder (P = 0.0393);
MVP		0.63
MPC		0.11
ClinPred		0.80	D
GERP RS		3.2
Varity_R		0.16
gMVP		0.51

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: chr11-31625337; COSMIC: COSV100635872; COSMIC: COSV100635872;