Variant 12-131960746-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015409.5(EP400):c.127G>A(p.Ala43Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000123 in 1,133,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., cov: 22)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

EP400
NM_015409.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.28

Variant links:

Genes affected

EP400 (HGNC:11958): (E1A binding protein p400) Predicted to enable several functions, including ATP binding activity; ATP-dependent chromatin remodeler activity; and protein antigen binding activity. Involved in histone H2A acetylation and histone H4 acetylation. Part of NuA4 histone acetyltransferase complex and Swr1 complex. [provided by Alliance of Genome Resources, Apr 2022]

EP400 links:

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=0.26187837).

BS2

High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EP400	NM_015409.5 linkuse as main transcript	c.127G>A	p.Ala43Thr	missense_variant	2/53	ENST00000389561.7	NP_056224.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EP400	ENST00000389561.7 linkuse as main transcript	c.127G>A	p.Ala43Thr	missense_variant	2/53	5	NM_015409.5	ENSP00000374212	P1	Q96L91-2
EP400	ENST00000333577.8 linkuse as main transcript	c.127G>A	p.Ala43Thr	missense_variant	2/13	1		ENSP00000333602
EP400	ENST00000332482.8 linkuse as main transcript	c.127G>A	p.Ala43Thr	missense_variant	2/8	1		ENSP00000331737
EP400	ENST00000703283.1 linkuse as main transcript	c.127G>A	p.Ala43Thr	missense_variant	1/11			ENSP00000515253

Frequencies

GnomAD3 genomes

AF:

0.0000206

AC:

AN:

96976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000813

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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:

0.00000945

AC:

AN:

211748

Hom.:

AF XY:

0.00

AC XY:

AN XY:

117378

show subpopulations

Gnomad AFR exome

AF:

0.0000762

Gnomad AMR exome

AF:

0.0000373

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1036754

Hom.:

Cov.:

AF XY:

0.00000794

AC XY:

AN XY:

503870

show subpopulations

Gnomad4 AFR exome

AF:

0.0000455

Gnomad4 AMR exome

AF:

0.0000361

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000195

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000939

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000206

AC:

AN:

96976

Hom.:

Cov.:

AF XY:

0.0000442

AC XY:

AN XY:

45240

show subpopulations

Gnomad4 AFR

AF:

0.0000813

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Apr 01, 2024

The c.127G>A (p.A43T) alteration is located in exon 2 (coding exon 1) of the EP400 gene. This alteration results from a G to A substitution at nucleotide position 127, causing the alanine (A) at amino acid position 43 to be replaced by a threonine (T). 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

BayesDel_addAF

Uncertain

0.080

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Benign

0.87

Eigen

Benign

0.12

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.84

T;T;T;.

M_CAP

Benign

0.068

MetaRNN

Benign

0.26

T;T;T;T

MetaSVM

Uncertain

0.28

MutationAssessor

Benign

1.2

L;.;.;L

MutationTaster

Benign

0.68

N;N;N;N;N;N;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.7

N;N;N;N

REVEL

Uncertain

0.38

Sift

Benign

0.031

D;D;D;D

Sift4G

Benign

0.11

T;T;T;T

Polyphen

0.75

P;.;.;P

Vest4

0.20

MVP

0.63

MPC

1.3

ClinPred

0.19

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.18

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.

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