Variant chr12-131960752-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015409.5(EP400):c.133T>C(p.Ser45Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 19)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EP400
NM_015409.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.45

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EP400	NM_015409.5 linkuse as main transcript	c.133T>C	p.Ser45Pro	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.133T>C	p.Ser45Pro	missense_variant	2/53	5	NM_015409.5	ENSP00000374212	P1	Q96L91-2
EP400	ENST00000333577.8 linkuse as main transcript	c.133T>C	p.Ser45Pro	missense_variant	2/13	1		ENSP00000333602
EP400	ENST00000332482.8 linkuse as main transcript	c.133T>C	p.Ser45Pro	missense_variant	2/8	1		ENSP00000331737
EP400	ENST00000703283.1 linkuse as main transcript	c.133T>C	p.Ser45Pro	missense_variant	1/11			ENSP00000515253

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

70758

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

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:

0.0000265

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1012264

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

491000

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000141

AC:

AN:

70758

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

32950

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000265

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000111

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

EP400-related disorder

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 15, 2023

The EP400 c.133T>C variant is predicted to result in the amino acid substitution p.Ser45Pro. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.068

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Benign

0.50

Eigen

Benign

0.043

Eigen_PC

Benign

-0.045

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.91

D;D;D;.

M_CAP

Uncertain

0.18

MetaRNN

Uncertain

0.46

T;T;T;T

MetaSVM

Uncertain

0.077

MutationAssessor

Benign

1.8

L;.;.;L

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-2.4

N;N;N;N

REVEL

Uncertain

0.39

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Uncertain

0.0020

D;T;T;D

Polyphen

0.87

P;.;.;P

Vest4

0.39

MVP

0.77

MPC

1.6

ClinPred

0.89

GERP RS

4.4

gMVP

0.16

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