Variant 15-43776783-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000319359.8(ELL3):c.119G>T(p.Cys40Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000145 in 1,605,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C40G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

ELL3
ENST00000319359.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.811

Variant links:

Genes affected

ELL3 (HGNC:23113): (elongation factor for RNA polymerase II 3) Predicted to enable cis-regulatory region sequence-specific DNA binding activity. Involved in positive regulation of transcription, DNA-templated and transcription by RNA polymerase II. Located in several cellular components, including chromosome; cytosol; and nuclear lumen. Part of transcription elongation factor complex. [provided by Alliance of Genome Resources, Apr 2022]

ELL3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.063574046).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELL3	NM_025165.3 linkuse as main transcript	c.119G>T	p.Cys40Phe	missense_variant	1/11	ENST00000319359.8	NP_079441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELL3	ENST00000319359.8 linkuse as main transcript	c.119G>T	p.Cys40Phe	missense_variant	1/11	1	NM_025165.3	ENSP00000320346	P1	Q9HB65-1
ELL3	ENST00000433927.1 linkuse as main transcript	c.209G>T	p.Cys70Phe	missense_variant	2/6	5		ENSP00000404209
ELL3	ENST00000486851.5 linkuse as main transcript	n.184G>T		non_coding_transcript_exon_variant	1/5	2
ELL3	ENST00000497700.1 linkuse as main transcript	n.186G>T		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152288

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000177

AC:

AN:

243278

Hom.:

AF XY:

0.000220

AC XY:

AN XY:

131796

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000207

Gnomad ASJ exome

AF:

0.00124

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000100

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000156

Gnomad OTH exome

AF:

0.000677

GnomAD4 exome

AF:

0.000147

AC:

213

AN:

1453458

Hom.:

Cov.:

AF XY:

0.000151

AC XY:

109

AN XY:

721554

show subpopulations

Gnomad4 AFR exome

AF:

0.0000902

Gnomad4 AMR exome

AF:

0.000249

Gnomad4 ASJ exome

AF:

0.00170

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000584

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000111

Gnomad4 OTH exome

AF:

0.000284

GnomAD4 genome

AF:

0.000131

AC:

AN:

152406

Hom.:

Cov.:

AF XY:

0.0000939

AC XY:

AN XY:

74532

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000326

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000131

Hom.:

Bravo

AF:

0.000174

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.119G>T (p.C40F) alteration is located in exon 1 (coding exon 1) of the ELL3 gene. This alteration results from a G to T substitution at nucleotide position 119, causing the cysteine (C) at amino acid position 40 to be replaced by a phenylalanine (F). 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

0.27

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0028

T;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.064

T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

0.73

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.39

N;N

REVEL

Benign

0.18

Sift

Benign

0.62

T;T

Sift4G

Uncertain

0.0080

D;.

Polyphen

1.0

D;.

Vest4

0.46

MVP

0.69

MPC

0.89

ClinPred

0.10

GERP RS

4.6

Varity_R

0.35

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over