rs386834178
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_StrongPP5
The NM_030943.4(AMN):c.761G>A(p.Gly254Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000775 in 1,549,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. G254G) has been classified as Likely benign.
Frequency
Consequence
NM_030943.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AMN | NM_030943.4 | c.761G>A | p.Gly254Glu | missense_variant, splice_region_variant | 8/12 | ENST00000299155.10 | |
AMN | XM_011537202.4 | c.599G>A | p.Gly200Glu | missense_variant, splice_region_variant | 8/12 | ||
AMN | XM_011537203.4 | c.599G>A | p.Gly200Glu | missense_variant, splice_region_variant | 8/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AMN | ENST00000299155.10 | c.761G>A | p.Gly254Glu | missense_variant, splice_region_variant | 8/12 | 1 | NM_030943.4 | P1 | |
AMN | ENST00000559789.1 | c.127-510G>A | intron_variant | 3 | |||||
AMN | ENST00000541086.5 | n.1507G>A | splice_region_variant, non_coding_transcript_exon_variant | 7/11 | 2 | ||||
AMN | ENST00000558590.1 | n.724G>A | splice_region_variant, non_coding_transcript_exon_variant | 3/9 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152204Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000716 AC: 10AN: 1397044Hom.: 0 Cov.: 33 AF XY: 0.00000726 AC XY: 5AN XY: 689094
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74372
ClinVar
Submissions by phenotype
Imerslund-Grasbeck syndrome Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at