chrX-24179237-CTG-C

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_003410.4(ZFX):​c.115_116delGT​(p.Val39PhefsTer14) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 23)

Consequence

ZFX
NM_003410.4 frameshift

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.68

Publications

0 publications found
Variant links:
Genes affected
ZFX (HGNC:12869): (zinc finger protein X-linked) This gene on the X chromosome is structurally similar to a related gene on the Y chromosome. It encodes a member of the krueppel C2H2-type zinc-finger protein family. The full-length protein contains an acidic transcriptional activation domain (AD), a nuclear localization sequence (NLS) and a DNA binding domain (DBD) consisting of 13 C2H2-type zinc fingers. Studies in mouse embryonic and adult hematopoietic stem cells showed that this gene was required as a transcriptional regulator for self-renewal of both stem cell types, but it was dispensable for growth and differentiation of their progeny. Multiple alternatively spliced transcript variants encoding different isoforms have been identified, but the full-length nature of some variants has not been determined. [provided by RefSeq, May 2010]
ZFX Gene-Disease associations (from GenCC):
  • intellectual developmental disorder, X-linked, syndromic 37
    Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

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ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 11 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant X-24179237-CTG-C is Pathogenic according to our data. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-24179237-CTG-C is described in CliVar as Pathogenic. Clinvar id is 3066053.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZFXNM_003410.4 linkc.115_116delGT p.Val39PhefsTer14 frameshift_variant Exon 5 of 10 ENST00000304543.10 NP_003401.2 P17010-1A0A024RC04Q8WXB7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZFXENST00000304543.10 linkc.115_116delGT p.Val39PhefsTer14 frameshift_variant Exon 5 of 10 5 NM_003410.4 ENSP00000304985.5 P17010-1

Frequencies

GnomAD3 genomes
Cov.:
23
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
23

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Intellectual developmental disorder, X-linked, syndromic 37 Pathogenic:1
Apr 02, 2024
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
7.7

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

Other links and lift over

hg19: chrX-24197354; COSMIC: COSV100458204; COSMIC: COSV100458204; API