NM_003640.5:c.3213G>C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_003640.5(ELP1):c.3213G>C(p.Glu1071Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000694 in 1,613,998 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. E1071E) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00055 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00071 ( 1 hom. )

Consequence

ELP1
NM_003640.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:6B:1

Conservation

PhyloP100: 0.934

Publications

5 publications found

Variant links:

Genes affected

ELP1 (HGNC:5959): (elongator acetyltransferase complex subunit 1) The protein encoded by this gene is a scaffold protein and a regulator for three different kinases involved in proinflammatory signaling. The encoded protein can bind NF-kappa-B-inducing kinase and I-kappa-B kinases through separate domains and assemble them into an active kinase complex. Mutations in this gene have been associated with familial dysautonomia. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

ELP1 Gene-Disease associations (from GenCC):

primary dysautonomia
Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
Riley-Day syndrome
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
medulloblastoma
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ELP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.023973256).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003640.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ELP1	NM_003640.5	MANE Select	c.3213G>C	p.Glu1071Asp	missense	Exon 29 of 37	NP_003631.2
ELP1	NM_001318360.2		c.2871G>C	p.Glu957Asp	missense	Exon 29 of 37	NP_001305289.1	A0A6Q8PGW3
ELP1	NM_001330749.2		c.2166G>C	p.Glu722Asp	missense	Exon 27 of 35	NP_001317678.1	F5H2T0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ELP1	ENST00000374647.10	TSL:1 MANE Select	c.3213G>C	p.Glu1071Asp	missense	Exon 29 of 37	ENSP00000363779.5	O95163
ELP1	ENST00000537196.1	TSL:1	c.2166G>C	p.Glu722Asp	missense	Exon 22 of 30	ENSP00000439367.1	F5H2T0
ELP1	ENST00000495759.6	TSL:1	n.*1823G>C		non_coding_transcript_exon	Exon 23 of 31	ENSP00000433514.2	H0YDF3

Frequencies

GnomAD3 genomes

AF:

0.000552

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000955

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000466

AC:

117

AN:

251280

AF XY:

0.000464

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000889

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000709

AC:

1036

AN:

1461772

Hom.:

Cov.:

AF XY:

0.000672

AC XY:

489

AN XY:

727184

show subpopulations

African (AFR)

AF:

0.000119

AC:

AN:

33476

American (AMR)

AF:

0.000246

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.000112

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000883

AC:

982

AN:

1111920

Other (OTH)

AF:

0.000530

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

103

155

206

258

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000552

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.000538

AC XY:

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.000338

AC:

AN:

41460

American (AMR)

AF:

0.000131

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.000207

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000955

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000880

Hom.:

Bravo

AF:

0.000495

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000486

AC:

EpiCase

AF:

0.00109

EpiControl

AF:

0.00107

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Familial dysautonomia (1)

Familial dysautonomia;C0025149:Medulloblastoma (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.055

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.46

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.82

M_CAP

Benign

0.010

MetaRNN

Benign

0.024

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

0.93

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.53

REVEL

Benign

0.025

Sift

Benign

0.43

Sift4G

Benign

0.83

Polyphen

0.0010

Vest4

0.18

MutPred

0.36

Gain of phosphorylation at Y1076 (P = 0.3664)

MVP

0.30

MPC

0.068

ClinPred

0.022

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.30

Mutation Taster

=85/15

polymorphism

(source)

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over