chrX-64190112-TG-T
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_152424.4(AMER1):c.3174del(p.Ser1059ValfsTer71) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000914 in 1,093,577 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 23)
Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )
Consequence
AMER1
NM_152424.4 frameshift
NM_152424.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.683
Genes affected
AMER1 (HGNC:26837): (APC membrane recruitment protein 1) The protein encoded by this gene upregulates trancriptional activation by the Wilms tumor protein and interacts with many other proteins, including CTNNB1, APC, AXIN1, and AXIN2. Defects in this gene are a cause of osteopathia striata with cranial sclerosis (OSCS). [provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0687 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AMER1 | NM_152424.4 | c.3174del | p.Ser1059ValfsTer71 | frameshift_variant | 2/2 | ENST00000374869.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AMER1 | ENST00000374869.8 | c.3174del | p.Ser1059ValfsTer71 | frameshift_variant | 2/2 | 5 | NM_152424.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000599 AC: 1AN: 166920Hom.: 0 AF XY: 0.0000182 AC XY: 1AN XY: 55062
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GnomAD4 exome AF: 9.14e-7 AC: 1AN: 1093577Hom.: 0 Cov.: 35 AF XY: 0.00000278 AC XY: 1AN XY: 359489
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GnomAD4 genome Cov.: 23
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 24, 2023 | This sequence change creates a premature translational stop signal (p.Ser1059Valfs*71) in the AMER1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 77 amino acid(s) of the AMER1 protein. This variant is present in population databases (no rsID available, gnomAD 0.004%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with AMER1-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at