chr14-102922722-CA-C
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Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_030943.4(AMN):c.35del(p.Gln12ArgfsTer5) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000111 in 1,439,678 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
AMN
NM_030943.4 frameshift
NM_030943.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.222
Genes affected
AMN (HGNC:14604): (amnion associated transmembrane protein) The protein encoded by this gene is a type I transmembrane protein. It is thought to modulate bone morphogenetic protein (BMP) receptor function by serving as an accessory or coreceptor, and thus facilitates or hinders BMP binding. It is known that the mouse AMN gene is expressed in the extraembryonic visceral endoderm layer during gastrulation, but it is found to be mutated in amnionless mouse. The encoded protein has sequence similarity to short gastrulation (Sog) and procollagen IIA proteins in Drosophila. [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 does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 37 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 14-102922722-CA-C is Pathogenic according to our data. Variant chr14-102922722-CA-C is described in ClinVar as [Pathogenic]. Clinvar id is 873125.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AMN | NM_030943.4 | c.35del | p.Gln12ArgfsTer5 | frameshift_variant | 1/12 | ENST00000299155.10 | |
AMN | XM_011537202.4 | c.-147del | 5_prime_UTR_variant | 1/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AMN | ENST00000299155.10 | c.35del | p.Gln12ArgfsTer5 | frameshift_variant | 1/12 | 1 | NM_030943.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000474 AC: 1AN: 211130Hom.: 0 AF XY: 0.00000872 AC XY: 1AN XY: 114666
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GnomAD4 exome AF: 0.0000111 AC: 16AN: 1439678Hom.: 0 Cov.: 32 AF XY: 0.0000126 AC XY: 9AN XY: 714516
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GnomAD4 genome Cov.: 33
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Imerslund-Grasbeck syndrome type 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 19, 2020 | - - |
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