11-31509876-G-C

Variant names:

• chr11-31509876-G-C
• rs1488836686
• NM_019040.5:c.92G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_019040.5(ELP4):​c.92G>C​(p.Arg31Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R31S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ELP4 NM_019040.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.67
• Publications: 0 publications found

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]

IMMP1L (HGNC:26317): (inner mitochondrial membrane peptidase subunit 1) The mitochondrial inner membrane peptidase (IMP) complex generates mature, active proteins in the mitochondrial intermembrane space by proteolytically removing the mitochondrial targeting presequence of nuclear-encoded proteins. IMP1 and IMP2 (IMMP2L; MIM 605977) are the catalytic subunits of the IMP complex (Burri et al., 2005 [PubMed 15814844]).[supplied by OMIM, Sep 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39611706).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019040.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELP4	NM_019040.5	MANE Select	c.92G>C	p.Arg31Thr	missense	Exon 1 of 10	NP_061913.3
	ELP4	NM_001288726.2		c.92G>C	p.Arg31Thr	missense	Exon 1 of 12	NP_001275655.1	G5E9D4
	ELP4	NM_001288725.2		c.92G>C	p.Arg31Thr	missense	Exon 1 of 11	NP_001275654.1	Q96EB1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELP4	ENST00000640961.2	TSL:1 MANE Select	c.92G>C	p.Arg31Thr	missense	Exon 1 of 10	ENSP00000492152.1	Q96EB1-1
	ELP4	ENST00000395934.2	TSL:1	c.92G>C	p.Arg31Thr	missense	Exon 1 of 12	ENSP00000379267.2	G5E9D4
	ELP4	ENST00000379163.10	TSL:2	c.92G>C	p.Arg31Thr	missense	Exon 1 of 11	ENSP00000368461.5	Q96EB1-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.94	D
M_CAP	Pathogenic	0.30	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.43	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		3.7
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.28
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.99	D
Vest4		0.54
MutPred		0.52		Loss of methylation at R31 (P = 0.0285)
MVP		0.64
MPC		0.38
ClinPred		0.99	D
GERP RS		4.7
PromoterAI		-0.029	Neutral
Varity_R		0.28
gMVP		0.72
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs1488836686; hg19: chr11-31531423;