Variant 12-131961041-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_015409.5(EP400):c.422C>T(p.Pro141Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000216 in 1,432,240 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000022 ( 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: 7.38

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 -4 ACMG points.

BS2

High AC in GnomAdExome4 at 31 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EP400	NM_015409.5 linkuse as main transcript	c.422C>T	p.Pro141Leu	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.422C>T	p.Pro141Leu	missense_variant	2/53	5	NM_015409.5	ENSP00000374212	P1	Q96L91-2
EP400	ENST00000333577.8 linkuse as main transcript	c.422C>T	p.Pro141Leu	missense_variant	2/13	1		ENSP00000333602
EP400	ENST00000332482.8 linkuse as main transcript	c.422C>T	p.Pro141Leu	missense_variant	2/8	1		ENSP00000331737
EP400	ENST00000703283.1 linkuse as main transcript	c.422C>T	p.Pro141Leu	missense_variant	1/11			ENSP00000515253

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151698

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000441

AC:

AN:

181210

Hom.:

AF XY:

0.0000408

AC XY:

AN XY:

98012

show subpopulations

Gnomad AFR exome

AF:

0.000103

Gnomad AMR exome

AF:

0.0000369

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000118

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000133

Gnomad OTH exome

AF:

0.000419

GnomAD4 exome

AF:

0.0000216

AC:

AN:

1432240

Hom.:

Cov.:

AF XY:

0.0000267

AC XY:

AN XY:

710334

show subpopulations

Gnomad4 AFR exome

AF:

0.0000305

Gnomad4 AMR exome

AF:

0.0000250

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000264

Gnomad4 SAS exome

AF:

0.0000722

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000182

Gnomad4 OTH exome

AF:

0.0000338

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000198

AC:

AN:

151698

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74044

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000844

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

Dec 28, 2023

The c.422C>T (p.P141L) alteration is located in exon 2 (coding exon 1) of the EP400 gene. This alteration results from a C to T substitution at nucleotide position 422, causing the proline (P) at amino acid position 141 to be replaced by a leucine (L). 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

Benign

-0.016

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

DANN

Benign

0.77

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;D;D;.

M_CAP

Pathogenic

0.34

MetaRNN

Uncertain

0.72

D;D;D;D

MetaSVM

Uncertain

0.74

MutationAssessor

Uncertain

2.0

M;.;.;M

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-4.4

D;D;D;D

REVEL

Uncertain

0.64

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D

Polyphen

1.0

D;.;.;D

Vest4

0.34

MVP

0.77

MPC

1.4

ClinPred

0.20

GERP RS

5.7

gMVP

0.25

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