11-31509801-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_019040.5(ELP4):​c.17C>T​(p.Thr6Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,614,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

ELP4
NM_019040.5 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:2

Conservation

PhyloP100: -0.248
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.07606763).
BS2
High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ELP4NM_019040.5 linkuse as main transcriptc.17C>T p.Thr6Ile missense_variant 1/10 ENST00000640961.2 NP_061913.3
ELP4NM_001288726.2 linkuse as main transcriptc.17C>T p.Thr6Ile missense_variant 1/12 NP_001275655.1
ELP4NM_001288725.2 linkuse as main transcriptc.17C>T p.Thr6Ile missense_variant 1/11 NP_001275654.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ELP4ENST00000640961.2 linkuse as main transcriptc.17C>T p.Thr6Ile missense_variant 1/101 NM_019040.5 ENSP00000492152 P3Q96EB1-1

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152238
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000241
AC:
6
AN:
249284
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135278
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000530
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000219
AC:
32
AN:
1461808
Hom.:
0
Cov.:
31
AF XY:
0.0000206
AC XY:
15
AN XY:
727190
show subpopulations
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:
0.0000288
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152238
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189
ExAC
AF:
0.00000826
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
Likely benign, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 13, 2023The c.17C>T (p.T6I) alteration is located in exon 1 (coding exon 1) of the ELP4 gene. This alteration results from a C to T substitution at nucleotide position 17, causing the threonine (T) at amino acid position 6 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
18
DANN
Uncertain
1.0
DEOGEN2
Benign
0.014
T;.;.;.;.;.;.;.;.;.;.;.;.
Eigen
Benign
-0.96
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.21
N
LIST_S2
Uncertain
0.86
D;D;D;D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
0.041
D
MetaRNN
Benign
0.076
T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.7
L;.;L;.;.;.;.;.;.;.;.;.;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-0.88
.;.;N;.;N;.;.;.;.;.;.;.;N
REVEL
Benign
0.020
Sift
Uncertain
0.0050
.;.;D;.;D;.;.;.;.;.;.;.;D
Sift4G
Uncertain
0.021
.;.;D;.;T;.;.;.;.;.;.;.;D
Polyphen
0.0020
B;.;.;.;.;.;.;.;.;.;.;.;B
Vest4
0.37, 0.39, 0.37
MutPred
0.30
Loss of glycosylation at T6 (P = 0.0101);Loss of glycosylation at T6 (P = 0.0101);Loss of glycosylation at T6 (P = 0.0101);Loss of glycosylation at T6 (P = 0.0101);Loss of glycosylation at T6 (P = 0.0101);Loss of glycosylation at T6 (P = 0.0101);Loss of glycosylation at T6 (P = 0.0101);Loss of glycosylation at T6 (P = 0.0101);Loss of glycosylation at T6 (P = 0.0101);Loss of glycosylation at T6 (P = 0.0101);Loss of glycosylation at T6 (P = 0.0101);Loss of glycosylation at T6 (P = 0.0101);Loss of glycosylation at T6 (P = 0.0101);
MVP
0.33
MPC
0.12
ClinPred
0.13
T
GERP RS
1.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.058
gMVP
0.33

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs760224399; hg19: chr11-31531348; API