rs373204347
Positions:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_030943.4(AMN):c.296-9C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000417 in 1,605,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000043 ( 0 hom. )
Consequence
AMN
NM_030943.4 splice_polypyrimidine_tract, intron
NM_030943.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.03461
2
Clinical Significance
Conservation
PhyloP100: -0.810
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 Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AMN | NM_030943.4 | c.296-9C>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000299155.10 | |||
AMN | XM_011537202.4 | c.134-9C>G | splice_polypyrimidine_tract_variant, intron_variant | ||||
AMN | XM_011537203.4 | c.134-9C>G | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AMN | ENST00000299155.10 | c.296-9C>G | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_030943.4 | P1 | |||
AMN | ENST00000558590.1 | n.105C>G | non_coding_transcript_exon_variant | 1/9 | 2 | ||||
AMN | ENST00000559442.1 | n.58C>G | non_coding_transcript_exon_variant | 1/3 | 2 | ||||
AMN | ENST00000541086.5 | n.1042-9C>G | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152174Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000420 AC: 10AN: 237820Hom.: 0 AF XY: 0.0000538 AC XY: 7AN XY: 130022
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GnomAD4 exome AF: 0.0000427 AC: 62AN: 1453278Hom.: 0 Cov.: 33 AF XY: 0.0000484 AC XY: 35AN XY: 723008
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GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152292Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4AN XY: 74454
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Imerslund-Grasbeck syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 20, 2022 | This sequence change falls in intron 4 of the AMN gene. It does not directly change the encoded amino acid sequence of the AMN protein. This variant is present in population databases (rs373204347, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with AMN-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: 9
Find out detailed SpliceAI scores and Pangolin per-transcript scores at