Variant X-104250380-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_153448.4(ESX1):c.1069C>G(p.Leu357Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000147 in 902,084 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 33 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., 7 hem., cov: 20)

Exomes 𝑓: 0.00015 ( 0 hom. 33 hem. )

Failed GnomAD Quality Control

Consequence

ESX1
NM_153448.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.29

Variant links:

Genes affected

ESX1 (HGNC:14865): (ESX homeobox 1) This gene encodes a dual-function 65 kDa protein that undergoes proteolytic cleavage to produce a 45 kDa N-terminal fragment with a paired-like homeodomain and a 20 kDa C-terminal fragment with a proline-rich domain. The C-terminal fragment localizes to the cytoplasm while the N-terminal fragment localizes exclusively to the nucleus. In contrast to human, the mouse homolog has a novel PN/PF motif in the C-terminus and is paternally imprinted in placental tissue. This gene likely plays a role in placental development and spermatogenesis. [provided by RefSeq, Jan 2010]

ESX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0078032017).

BP6

Variant X-104250380-G-C is Benign according to our data. Variant chrX-104250380-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2661111.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 33 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESX1	NM_153448.4 linkuse as main transcript	c.1069C>G	p.Leu357Val	missense_variant	4/4	ENST00000372588.4	NP_703149.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESX1	ENST00000372588.4 linkuse as main transcript	c.1069C>G	p.Leu357Val	missense_variant	4/4	1	NM_153448.4	ENSP00000361669	P1

Frequencies

GnomAD3 genomes

AF:

0.000390

AC:

AN:

92357

Hom.:

Cov.:

AF XY:

0.000287

AC XY:

AN XY:

24419

show subpopulations

Gnomad AFR

AF:

0.000115

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00127

Gnomad ASJ

AF:

0.000883

Gnomad EAS

AF:

0.000376

Gnomad SAS

AF:

0.000543

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000378

Gnomad OTH

AF:

0.000821

GnomAD3 exomes

AF:

0.000605

AC:

AN:

38002

Hom.:

AF XY:

0.00

AC XY:

AN XY:

5990

show subpopulations

Gnomad AFR exome

AF:

0.000406

Gnomad AMR exome

AF:

0.000330

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000711

Gnomad FIN exome

AF:

0.000489

Gnomad NFE exome

AF:

0.000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000147

AC:

133

AN:

902084

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

278806

show subpopulations

Gnomad4 AFR exome

AF:

0.0000538

Gnomad4 AMR exome

AF:

0.000445

Gnomad4 ASJ exome

AF:

0.0000849

Gnomad4 EAS exome

AF:

0.000137

Gnomad4 SAS exome

AF:

0.000131

Gnomad4 FIN exome

AF:

0.000459

Gnomad4 NFE exome

AF:

0.000123

Gnomad4 OTH exome

AF:

0.000350

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000390

AC:

AN:

92368

Hom.:

Cov.:

AF XY:

0.000286

AC XY:

AN XY:

24446

show subpopulations

Gnomad4 AFR

AF:

0.000115

Gnomad4 AMR

AF:

0.00126

Gnomad4 ASJ

AF:

0.000883

Gnomad4 EAS

AF:

0.000377

Gnomad4 SAS

AF:

0.000546

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000378

Gnomad4 OTH

AF:

0.000814

Alfa

AF:

0.00769

Hom.:

ExAC

AF:

0.000577

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

ESX1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.020

DANN

Benign

0.12

DEOGEN2

Benign

0.055

FATHMM_MKL

Benign

0.0010

LIST_S2

Benign

0.61

M_CAP

Benign

0.0020

MetaRNN

Benign

0.0078

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.90

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.14

REVEL

Benign

0.075

Sift

Benign

0.30

Sift4G

Benign

0.61

Polyphen

0.0

Vest4

0.054

MVP

0.15

MPC

0.41

ClinPred

0.0090

GERP RS

-4.3

Varity_R

0.042

gMVP

0.048

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