NM_019040.5:c.488G>T

Variant names:

• chr11-31594876-G-T
• NM_019040.5:c.488G>T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_019040.5(ELP4):​c.488G>T​(p.Arg163Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,408,052 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: 8.48

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.973

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP4	NM_019040.5	c.488G>T	p.Arg163Leu	missense_variant	Exon 4 of 10	ENST00000640961.2	NP_061913.3
ELP4	NM_001288726.2	c.488G>T	p.Arg163Leu	missense_variant	Exon 4 of 12		NP_001275655.1
ELP4	NM_001288725.2	c.488G>T	p.Arg163Leu	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.488G>T	p.Arg163Leu	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: 1408052 Hom.: 0 Cov.: 29 AF XY: 0.00000143 AC XY: 1 AN XY: 698874

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: 0.00

Gnomad4 OTH exome AF: 0.0000172

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T;.;.;.;.;.;.;.;.;.;.;.
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.97	D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.26	D
MutationAssessor	Pathogenic	3.8	H;.;H;.;.;.;.;.;.;.;.;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-6.8	.;.;D;.;D;.;.;.;.;.;.;D
REVEL	Pathogenic	0.78
Sift	Pathogenic	0.0	.;.;D;.;D;.;.;.;.;.;.;D
Sift4G	Uncertain	0.0020	.;.;D;.;D;.;.;.;.;.;.;D
Polyphen		1.0	D;.;.;.;.;.;.;.;.;.;.;D
Vest4		0.92, 0.96, 0.96
MutPred		0.90		Loss of catalytic residue at R163 (P = 0.0123);Loss of catalytic residue at R163 (P = 0.0123);Loss of catalytic residue at R163 (P = 0.0123);Loss of catalytic residue at R163 (P = 0.0123);Loss of catalytic residue at R163 (P = 0.0123);Loss of catalytic residue at R163 (P = 0.0123);Loss of catalytic residue at R163 (P = 0.0123);Loss of catalytic residue at R163 (P = 0.0123);Loss of catalytic residue at R163 (P = 0.0123);Loss of catalytic residue at R163 (P = 0.0123);Loss of catalytic residue at R163 (P = 0.0123);Loss of catalytic residue at R163 (P = 0.0123);
MVP		0.88
MPC		0.37
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.86
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr11-31616423;