chr11-31539674-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP5BS2_Supporting

The NM_019040.5(ELP4):ā€‹c.272A>Gā€‹(p.Tyr91Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000934 in 1,606,052 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: š‘“ 0.000033 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000069 ( 0 hom. )

Consequence

ELP4
NM_019040.5 missense

Scores

2
11
6

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 5.17
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PP5
Variant 11-31539674-A-G is Pathogenic according to our data. Variant chr11-31539674-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1328942.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
High AC in GnomAd4 at 5 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ELP4NM_019040.5 linkuse as main transcriptc.272A>G p.Tyr91Cys missense_variant 3/10 ENST00000640961.2 NP_061913.3
ELP4NM_001288726.2 linkuse as main transcriptc.272A>G p.Tyr91Cys missense_variant 3/12 NP_001275655.1
ELP4NM_001288725.2 linkuse as main transcriptc.272A>G p.Tyr91Cys missense_variant 3/11 NP_001275654.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ELP4ENST00000640961.2 linkuse as main transcriptc.272A>G p.Tyr91Cys missense_variant 3/101 NM_019040.5 ENSP00000492152 P3Q96EB1-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152170
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000770
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000573
AC:
14
AN:
244216
Hom.:
0
AF XY:
0.0000604
AC XY:
8
AN XY:
132348
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000788
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000688
AC:
10
AN:
1453764
Hom.:
0
Cov.:
30
AF XY:
0.00000692
AC XY:
5
AN XY:
722694
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000253
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152288
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000965
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.0000497
AC:
6
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Seizure;C0338656:Cognitive impairment;C0557874:Global developmental delay Pathogenic:1
Likely pathogenic, no assertion criteria providedclinical testingWainwright Lab, University Of Queensland-The variant is inherited in compound heterozygosity: c.886C>A (p.Leu296Ile) (inherited from mother) and c.272A>G (p.Tyr91Cys) (inherited from the father). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Benign
-0.061
T
BayesDel_noAF
Uncertain
0.060
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
T;.;.;.;.;.;.;.;.;.;.;.
Eigen
Uncertain
0.68
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Pathogenic
0.98
D;D;D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
0.042
D
MetaRNN
Uncertain
0.59
D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.54
T
MutationAssessor
Uncertain
2.8
M;.;M;.;.;.;.;.;.;.;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.69
T
PROVEAN
Pathogenic
-5.4
.;.;D;.;D;.;.;.;.;.;.;D
REVEL
Uncertain
0.39
Sift
Uncertain
0.013
.;.;D;.;D;.;.;.;.;.;.;D
Sift4G
Uncertain
0.0080
.;.;D;.;D;.;.;.;.;.;.;D
Polyphen
1.0
D;.;.;.;.;.;.;.;.;.;.;D
Vest4
0.71, 0.68, 0.67
MutPred
0.65
Loss of ubiquitination at K90 (P = 0.0795);Loss of ubiquitination at K90 (P = 0.0795);Loss of ubiquitination at K90 (P = 0.0795);Loss of ubiquitination at K90 (P = 0.0795);Loss of ubiquitination at K90 (P = 0.0795);Loss of ubiquitination at K90 (P = 0.0795);Loss of ubiquitination at K90 (P = 0.0795);Loss of ubiquitination at K90 (P = 0.0795);Loss of ubiquitination at K90 (P = 0.0795);Loss of ubiquitination at K90 (P = 0.0795);Loss of ubiquitination at K90 (P = 0.0795);Loss of ubiquitination at K90 (P = 0.0795);
MVP
0.72
MPC
0.36
ClinPred
0.74
D
GERP RS
5.3
Varity_R
0.57
gMVP
0.62

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

LitVar

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

Other links and lift over

dbSNP: rs758883150; hg19: chr11-31561221; API