Genetic Variant ELP4:p.Gln165Leu (chr11-31594882-A-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q165P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

ELP4
NM_019040.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.91

Publications

0 publications found

Variant links:

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]

ELP4 Gene-Disease associations (from GenCC):

aniridia 2
Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Genomics England PanelApp
aniridia 1
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ELP4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 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 link	c.494A>T	p.Gln165Leu	missense_variant	Exon 4 of 10	ENST00000640961.2	NP_061913.3	Q96EB1-1
ELP4	NM_001288726.2 link	c.494A>T	p.Gln165Leu	missense_variant	Exon 4 of 12		NP_001275655.1	Q96EB1G5E9D4
ELP4	NM_001288725.2 link	c.494A>T	p.Gln165Leu	missense_variant	Exon 4 of 11		NP_001275654.1	Q96EB1-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP4	ENST00000640961.2 link	c.494A>T	p.Gln165Leu	missense_variant	Exon 4 of 10	1	NM_019040.5	ENSP00000492152.1		Q96EB1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.10e-7

AC:

AN:

1407920

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

698832

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30128

American (AMR)

AF:

0.00

AC:

AN:

31500

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24848

East Asian (EAS)

AF:

0.00

AC:

AN:

36836

South Asian (SAS)

AF:

0.00

AC:

AN:

73798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53026

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5650

European-Non Finnish (NFE)

AF:

9.14e-7

AC:

AN:

1093966

Other (OTH)

AF:

0.00

AC:

AN:

58168

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

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

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

T;.;.;.;.;.;.;.;.;.;.;.

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

D;D;D;D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.061

MetaRNN

Pathogenic

0.79

D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.31

MutationAssessor

Pathogenic

3.4

M;.;M;.;.;.;.;.;.;.;.;.

PhyloP100

7.9

PrimateAI

Benign

0.47

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

GERP RS

5.1

Varity_R

0.73

gMVP

0.57

Mutation Taster

=54/46

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over