X-110317617-C-CG
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Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_015365.3(AMMECR1):c.454_455insC(p.Arg152ProfsTer47) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 22)
Consequence
AMMECR1
NM_015365.3 frameshift
NM_015365.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.21
Genes affected
AMMECR1 (HGNC:467): (AMMECR nuclear protein 1) The exact function of this gene is not known, however, submicroscopic deletion of the X chromosome including this gene, COL4A5, and FACL4 genes, result in a contiguous gene deletion syndrome, the AMME complex (Alport syndrome, mental retardation, midface hypoplasia, and elliptocytosis). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 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-110317617-C-CG is Pathogenic according to our data. Variant chrX-110317617-C-CG is described in ClinVar as [Pathogenic]. Clinvar id is 817076.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AMMECR1 | NM_015365.3 | c.454_455insC | p.Arg152ProfsTer47 | frameshift_variant | 1/6 | ENST00000262844.10 | |
AMMECR1 | NM_001025580.2 | c.454_455insC | p.Arg152ProfsTer10 | frameshift_variant | 1/5 | ||
AMMECR1 | NM_001171689.2 | c.85_86insC | p.Arg29ProfsTer47 | frameshift_variant | 3/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AMMECR1 | ENST00000262844.10 | c.454_455insC | p.Arg152ProfsTer47 | frameshift_variant | 1/6 | 1 | NM_015365.3 | A1 |
Frequencies
GnomAD3 genomes Cov.: 22
GnomAD3 genomes
Cov.:
22
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 22
GnomAD4 genome
Cov.:
22
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Department of Endocrinology and Genetics, Fuzhou Children’s Hospital of Fujian Medical University | Jul 11, 2023 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Apr 07, 2020 | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is not a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
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Calibrated prediction
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Prediction
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at