rs1366977126
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5
The NM_000481.4(AMT):āc.515T>Cā(p.Leu172Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. L172L) has been classified as Likely benign.
Frequency
Consequence
NM_000481.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AMT | NM_000481.4 | c.515T>C | p.Leu172Pro | missense_variant | 5/9 | ENST00000273588.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AMT | ENST00000273588.9 | c.515T>C | p.Leu172Pro | missense_variant | 5/9 | 1 | NM_000481.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461886Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727246
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Non-ketotic hyperglycinemia Pathogenic:1Uncertain:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 27, 2023 | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 172 of the AMT protein (p.Leu172Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with nonketotic hyperglycinemia (PMID: 26179960; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 558446). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on AMT protein function. For these reasons, this variant has been classified as Pathogenic. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | May 22, 2018 | - - |
Glycine encephalopathy 1 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jan 02, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at