rs12883949
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_030943.4(AMN):c.761-1G>A variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
AMN
NM_030943.4 splice_acceptor, intron
NM_030943.4 splice_acceptor, intron
Scores
1
2
4
Splicing: ADA: 1.000
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.99
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 10 ACMG points.
PVS1
Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AMN | NM_030943.4 | c.761-1G>A | splice_acceptor_variant, intron_variant | ENST00000299155.10 | NP_112205.2 | |||
AMN | XM_011537202.4 | c.599-1G>A | splice_acceptor_variant, intron_variant | |||||
AMN | XM_011537203.4 | c.599-1G>A | splice_acceptor_variant, intron_variant | XP_011535505.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AMN | ENST00000299155.10 | c.761-1G>A | splice_acceptor_variant, intron_variant | 1 | NM_030943.4 | ENSP00000299155.6 | ||||
AMN | ENST00000559789.1 | c.125-511G>A | intron_variant | 3 | ENSP00000452831.1 | |||||
AMN | ENST00000541086.5 | n.1507-1G>A | splice_acceptor_variant, intron_variant | 2 | ||||||
AMN | ENST00000558590.1 | n.724-1G>A | splice_acceptor_variant, intron_variant | 2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1397010Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 689084
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1397010
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
689084
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
Alfa
AF:
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ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Benign
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 2
DS_AL_spliceai
Position offset: 1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at