dbSNP rs1556393718: ESX1:p.Gly342_Pro377del (chrX-104250317-TGGGTGGCAGAGGCGCCATGGGCGGCCCGGGTGGCAGAGGCGCCATGGGCGGCCCGGGTGGCAGAGGCGCCATGGGCGGCCCGGGTGGCAGAGGCGCCATGGGCGGCCC-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_153448.4(ESX1):c.1024_1131del(p.Gly342_Pro377del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000809 in 98,923 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000081 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000021 ( 0 hom. 7 hem. )

Failed GnomAD Quality Control

Consequence

ESX1
NM_153448.4 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.38

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_153448.4.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153448.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESX1	NM_153448.4	MANE Select	c.1024_1131del	p.Gly342_Pro377del	conservative_inframe_deletion	Exon 4 of 4	NP_703149.1	Q8N693

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESX1	ENST00000372588.4	TSL:1 MANE Select	c.1024_1131del	p.Gly342_Pro377del	conservative_inframe_deletion	Exon 4 of 4	ENSP00000361669.4	Q8N693

Frequencies

GnomAD3 genomes

AF:

0.0000809

AC:

AN:

98923

Hom.:

Cov.:

show subpopulations

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:

0.000164

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000211

AC:

AN:

1044007

Hom.:

AF XY:

0.0000210

AC XY:

AN XY:

332603

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23029

American (AMR)

AF:

0.00

AC:

AN:

29709

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17696

East Asian (EAS)

AF:

0.00

AC:

AN:

25377

South Asian (SAS)

AF:

0.00

AC:

AN:

47840

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38430

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3443

European-Non Finnish (NFE)

AF:

0.0000270

AC:

AN:

815350

Other (OTH)

AF:

0.00

AC:

AN:

43133

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000809

AC:

AN:

98923

Hom.:

Cov.:

AF XY:

0.0000360

AC XY:

AN XY:

27749

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26105

American (AMR)

AF:

0.00

AC:

AN:

9193

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2465

East Asian (EAS)

AF:

0.00

AC:

AN:

3049

South Asian (SAS)

AF:

0.00

AC:

AN:

2298

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4982

Middle Eastern (MID)

AF:

0.00

AC:

AN:

210

European-Non Finnish (NFE)

AF:

0.000164

AC:

AN:

48671

Other (OTH)

AF:

0.00

AC:

AN:

1312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.4

Mutation Taster

=184/16

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over