chr3-49420215-ATGAGGGCCAAATCTT-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM2PM4PP5_Very_Strong
The NM_000481.4(AMT):c.452_466delAAGATTTGGCCCTCA(p.Lys151_Leu155del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000112 in 1,614,054 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_000481.4 disruptive_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AMT | NM_000481.4 | c.452_466delAAGATTTGGCCCTCA | p.Lys151_Leu155del | disruptive_inframe_deletion | Exon 4 of 9 | ENST00000273588.9 | NP_000472.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AMT | ENST00000273588.9 | c.452_466delAAGATTTGGCCCTCA | p.Lys151_Leu155del | disruptive_inframe_deletion | Exon 4 of 9 | 1 | NM_000481.4 | ENSP00000273588.3 | ||
ENSG00000283189 | ENST00000636166.1 | c.689_703delAAGATTTGGCCCTCA | p.Lys230_Leu234del | disruptive_inframe_deletion | Exon 6 of 11 | 5 | ENSP00000490106.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251476Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135920
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461872Hom.: 0 AF XY: 0.0000110 AC XY: 8AN XY: 727238
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74344
ClinVar
Submissions by phenotype
Glycine encephalopathy Pathogenic:3
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This variant, c.452_466del, results in the deletion of 5 amino acid(s) of the AMT protein (p.Lys151_Leu155del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs386833683, gnomAD 0.006%). This variant has been observed in individual(s) with glycine encephalopathy (PMID: 16450403, 27362913). ClinVar contains an entry for this variant (Variation ID: 56232). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. For these reasons, this variant has been classified as Pathogenic. -
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Glycine encephalopathy 2 Pathogenic:3
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Neurodevelopmental delay Pathogenic:1
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not provided Pathogenic:1
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Glycine encephalopathy 1 Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at