NM_019040.5:c.130C>A

Variant names:

• chr11-31509914-C-A
• NM_019040.5:c.130C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.108

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 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
ELP4	NM_019040.5	c.130C>A	p.Pro44Thr	missense_variant	Exon 1 of 10	ENST00000640961.2	NP_061913.3
ELP4	NM_001288726.2	c.130C>A	p.Pro44Thr	missense_variant	Exon 1 of 12		NP_001275655.1
ELP4	NM_001288725.2	c.130C>A	p.Pro44Thr	missense_variant	Exon 1 of 11		NP_001275654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP4	ENST00000640961.2	c.130C>A	p.Pro44Thr	missense_variant	Exon 1 of 10	1	NM_019040.5	ENSP00000492152.1

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

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;