Variant X-104250317-TGGGTGGCAGAGGCGCCATGGGCGGCCCGGGTGGCAGAGGCGCCATGGGCGGCCC-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4BP6_ModerateBS2

The ENST00000372588.4(ESX1):c.1078_1131del(p.Gly360_Pro377del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000245 in 1,142,918 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000061 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000021 ( 0 hom. 12 hem. )

Consequence

ESX1
ENST00000372588.4 inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.38

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 Likely_benign. Variant got -4 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in ENST00000372588.4.

BP6

Variant X-104250317-TGGGTGGCAGAGGCGCCATGGGCGGCCCGGGTGGCAGAGGCGCCATGGGCGGCCC-T is Benign according to our data. Variant chrX-104250317-TGGGTGGCAGAGGCGCCATGGGCGGCCCGGGTGGCAGAGGCGCCATGGGCGGCCC-T is described in ClinVar as [Likely_benign]. Clinvar id is 2661110.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESX1	NM_153448.4 linkuse as main transcript	c.1078_1131del	p.Gly360_Pro377del	inframe_deletion	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.1078_1131del	p.Gly360_Pro377del	inframe_deletion	4/4	1	NM_153448.4	ENSP00000361669	P1

Frequencies

GnomAD3 genomes

AF:

0.0000607

AC:

AN:

98917

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

27749

show subpopulations

Gnomad AFR

AF:

0.000115

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:

0.000201

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000411

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000672

AC:

AN:

148813

Hom.:

AF XY:

0.00

AC XY:

AN XY:

49547

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000146

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000211

AC:

AN:

1044001

Hom.:

AF XY:

0.0000361

AC XY:

AN XY:

332597

show subpopulations

Gnomad4 AFR exome

AF:

0.0000434

Gnomad4 AMR exome

AF:

0.0000337

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000209

Gnomad4 FIN exome

AF:

0.0000260

Gnomad4 NFE exome

AF:

0.0000208

Gnomad4 OTH exome

AF:

0.0000232

GnomAD4 genome

AF:

0.0000607

AC:

AN:

98917

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

27749

show subpopulations

Gnomad4 AFR

AF:

0.000115

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000201

Gnomad4 NFE

AF:

0.0000411

Gnomad4 OTH

AF:

0.00

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

Oct 01, 2023

ESX1: PM4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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