Genetic Variant ELP4:p.Met170Arg (chr11-31594897-T-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_019040.5(ELP4):c.509T>G(p.Met170Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000713 in 1,401,588 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. M170T) 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: 5.12

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP4	NM_019040.5 link	c.509T>G	p.Met170Arg	missense_variant	Exon 4 of 10	ENST00000640961.2	NP_061913.3	Q96EB1-1
ELP4	NM_001288726.2 link	c.509T>G	p.Met170Arg	missense_variant	Exon 4 of 12		NP_001275655.1	Q96EB1G5E9D4
ELP4	NM_001288725.2 link	c.509T>G	p.Met170Arg	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.509T>G	p.Met170Arg	missense_variant	Exon 4 of 10	1	NM_019040.5	ENSP00000492152.1		Q96EB1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.13e-7

AC:

AN:

1401588

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

695732

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29640

American (AMR)

AF:

0.00

AC:

AN:

29126

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24552

East Asian (EAS)

AF:

0.0000272

AC:

AN:

36708

South Asian (SAS)

AF:

0.00

AC:

AN:

73000

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52920

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5628

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1092126

Other (OTH)

AF:

0.00

AC:

AN:

57888

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

0.19

BayesDel_addAF

Uncertain

0.066

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.081

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

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.82

T;T;T;T;T;T;T;T;T;T;T;T

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.57

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

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.8

L;.;L;.;.;.;.;.;.;.;.;.

PhyloP100

5.1

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-2.7

.;.;D;.;D;.;.;.;.;.;.;D

REVEL

Benign

0.24

Sift

Benign

0.080

.;.;T;.;D;.;.;.;.;.;.;T

Sift4G

Uncertain

0.039

.;.;D;.;T;.;.;.;.;.;.;D

Polyphen

0.82

P;.;.;.;.;.;.;.;.;.;.;D

Vest4

0.57, 0.55, 0.57

MutPred

0.69

Gain of MoRF binding (P = 0.0196);Gain of MoRF binding (P = 0.0196);Gain of MoRF binding (P = 0.0196);Gain of MoRF binding (P = 0.0196);Gain of MoRF binding (P = 0.0196);Gain of MoRF binding (P = 0.0196);Gain of MoRF binding (P = 0.0196);Gain of MoRF binding (P = 0.0196);Gain of MoRF binding (P = 0.0196);Gain of MoRF binding (P = 0.0196);Gain of MoRF binding (P = 0.0196);Gain of MoRF binding (P = 0.0196);

MVP

0.64

MPC

0.24

ClinPred

0.97

GERP RS

5.1

Varity_R

0.73

gMVP

0.59

Mutation Taster

=58/42

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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