Genetic Variant ESX1:p.Gly360_Pro377del (chrX-104250317-TGGGTGGCAGAGGCGCCATGGGCGGCCCGGGTGGCAGAGGCGCCATGGGCGGCCC-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM4BP6_ModerateBS2

The NM_153448.4(ESX1):c.1078_1131delGGGCCGCCCATGGCGCCTCTGCCACCCGGGCCGCCCATGGCGCCTCTGCCACCC(p.Gly360_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 0.0000245 in 1,142,918 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 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. 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
NM_153448.4 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_153448.4.

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 VariationId is 2661110.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 12 gene

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.1078_1131delGGGCCGCCCATGGCGCCTCTGCCACCCGGGCCGCCCATGGCGCCTCTGCCACCC	p.Gly360_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.1078_1131delGGGCCGCCCATGGCGCCTCTGCCACCCGGGCCGCCCATGGCGCCTCTGCCACCC	p.Gly360_Pro377del	conservative_inframe_deletion	Exon 4 of 4	ENSP00000361669.4	Q8N693

Frequencies

GnomAD3 genomes

AF:

0.0000607

AC:

AN:

98917

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.00000672

AC:

AN:

148813

AF XY:

0.00

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 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

African (AFR)

AF:

0.0000434

AC:

AN:

23029

American (AMR)

AF:

0.0000337

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:

0.0000209

AC:

AN:

47838

European-Finnish (FIN)

AF:

0.0000260

AC:

AN:

38430

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3443

European-Non Finnish (NFE)

AF:

0.0000208

AC:

AN:

815346

Other (OTH)

AF:

0.0000232

AC:

AN:

43133

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.0000607

AC:

AN:

98917

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

27749

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000115

AC:

AN:

26103

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:

0.000201

AC:

AN:

4982

Middle Eastern (MID)

AF:

0.00

AC:

AN:

210

European-Non Finnish (NFE)

AF:

0.0000411

AC:

AN:

48667

Other (OTH)

AF:

0.00

AC:

AN:

1312

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000896614), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.392

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.4

Mutation Taster

=195/5

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over