Genetic Variant NM_003640.5:c.536C>G (chr9-108922858-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_003640.5(ELP1):c.536C>G(p.Ala179Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 1,461,396 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 (★★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

ELP1
NM_003640.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 7.42

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

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.536C>G	p.Ala179Gly	missense	Exon 6 of 37	NP_003631.2
ELP1	NM_001318360.2		c.194C>G	p.Ala65Gly	missense	Exon 6 of 37	NP_001305289.1	A0A6Q8PGW3
ELP1	NM_001330749.2		c.-324C>G		5_prime_UTR	Exon 6 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.536C>G	p.Ala179Gly	missense	Exon 6 of 37	ENSP00000363779.5	O95163
ELP1	ENST00000537196.1	TSL:1	c.-307-5188C>G		intron	N/A	ENSP00000439367.1	F5H2T0
ELP1	ENST00000495759.6	TSL:1	n.536C>G		non_coding_transcript_exon	Exon 6 of 31	ENSP00000433514.2	H0YDF3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000557

AC:

AN:

251422

AF XY:

0.0000442

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000890

AC:

AN:

1461396

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727062

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.000291

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111592

Other (OTH)

AF:

0.00

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.437

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000741

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Familial dysautonomia (1)

Familial dysautonomia;C0025149:Medulloblastoma (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.40

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.75

M_CAP

Benign

0.038

MetaRNN

Benign

0.40

MetaSVM

Benign

-0.62

MutationAssessor

Pathogenic

3.4

PhyloP100

7.4

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.24

Sift

Uncertain

0.014

Sift4G

Uncertain

0.011

Polyphen

1.0

Vest4

0.35

MutPred

0.56

Loss of stability (P = 0.0569)

MVP

0.58

MPC

0.39

ClinPred

0.95

GERP RS

4.7

Varity_R

0.23

gMVP

0.43

Mutation Taster

=70/30

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.30

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.30

Position offset: -16

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over