X-11298274-AC-A
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001142.2(AMELX):c.143del(p.Pro48ArgfsTer47) variant causes a frameshift, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 23)
Consequence
AMELX
NM_001142.2 frameshift, splice_region
NM_001142.2 frameshift, splice_region
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.74
Genes affected
AMELX (HGNC:461): (amelogenin X-linked) This gene encodes a member of the amelogenin family of extracellular matrix proteins. Amelogenins are involved in biomineralization during tooth enamel development. Mutations in this gene cause X-linked amelogenesis imperfecta. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
ARHGAP6 (HGNC:676): (Rho GTPase activating protein 6) This gene encodes a member of the rhoGAP family of proteins which play a role in the regulation of actin polymerization at the plasma membrane during several cellular processes. This protein is thought to have two independent functions, one as a GTPase-activating protein with specificity for RhoA, and another as a cytoskeletal protein that promotes actin remodeling. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 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-11298274-AC-A is Pathogenic according to our data. Variant chrX-11298274-AC-A is described in ClinVar as [Pathogenic]. Clinvar id is 617639.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AMELX | NM_001142.2 | c.143del | p.Pro48ArgfsTer47 | frameshift_variant, splice_region_variant | 4/6 | ENST00000380714.7 | |
ARHGAP6 | NM_013427.3 | c.589-43568del | intron_variant | ENST00000337414.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AMELX | ENST00000380714.7 | c.143del | p.Pro48ArgfsTer47 | frameshift_variant, splice_region_variant | 4/6 | 1 | NM_001142.2 | P1 | |
ARHGAP6 | ENST00000337414.9 | c.589-43568del | intron_variant | 1 | NM_013427.3 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Amelogenesis imperfecta Pathogenic:1
Pathogenic, no assertion criteria provided | research | The Fourth Military Medical University, School of Stomatology | Jul 24, 2018 | The proband presented with small teeth having a generalized yellow color and thin rough enamel surfaces. Her father had similar findings and a partial denture. Her mother had multiple vertical cracks and uneven white color of her tooth enamel. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at