11-31594882-A-T

Variant names:

• chr11-31594882-A-T
• NM_019040.5:c.494A>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_019040.5(ELP4):​c.494A>T​(p.Gln165Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ELP4 NM_019040.5 missense
• Clinical Significance: Not reported in ClinVar
• 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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.79

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP4	NM_019040.5	c.494A>T	p.Gln165Leu	missense_variant	Exon 4 of 10	ENST00000640961.2	NP_061913.3
ELP4	NM_001288726.2	c.494A>T	p.Gln165Leu	missense_variant	Exon 4 of 12		NP_001275655.1
ELP4	NM_001288725.2	c.494A>T	p.Gln165Leu	missense_variant	Exon 4 of 11		NP_001275654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP4	ENST00000640961.2	c.494A>T	p.Gln165Leu	missense_variant	Exon 4 of 10	1	NM_019040.5	ENSP00000492152.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.10e-7 AC: 1 AN: 1407920 Hom.: 0 Cov.: 30 AF XY: 0.00000143 AC XY: 1 AN XY: 698832

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.14e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T;.;.;.;.;.;.;.;.;.;.;.
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.061	D
MetaRNN	Pathogenic	0.79	D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.31	T
MutationAssessor	Pathogenic	3.4	M;.;M;.;.;.;.;.;.;.;.;.
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-6.2	.;.;D;.;D;.;.;.;.;.;.;D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0030	.;.;D;.;D;.;.;.;.;.;.;D
Sift4G	Uncertain	0.0020	.;.;D;.;D;.;.;.;.;.;.;D
Polyphen		1.0	D;.;.;.;.;.;.;.;.;.;.;D
Vest4		0.61, 0.68, 0.70
MutPred		0.58		Loss of methylation at K169 (P = 0.0674);Loss of methylation at K169 (P = 0.0674);Loss of methylation at K169 (P = 0.0674);Loss of methylation at K169 (P = 0.0674);Loss of methylation at K169 (P = 0.0674);Loss of methylation at K169 (P = 0.0674);Loss of methylation at K169 (P = 0.0674);Loss of methylation at K169 (P = 0.0674);Loss of methylation at K169 (P = 0.0674);Loss of methylation at K169 (P = 0.0674);Loss of methylation at K169 (P = 0.0674);Loss of methylation at K169 (P = 0.0674);
MVP		0.78
MPC		0.33
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.73
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr11-31616429;