chr3-49417550-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000481.4(AMT):c.1202C>A(p.Thr401Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,614,042 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T401T) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AMT | NM_000481.4 | c.1202C>A | p.Thr401Asn | missense_variant | 9/9 | ENST00000273588.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AMT | ENST00000273588.9 | c.1202C>A | p.Thr401Asn | missense_variant | 9/9 | 1 | NM_000481.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152148Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251468Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135916
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461894Hom.: 1 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727248
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152148Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74332
ClinVar
Submissions by phenotype
Non-ketotic hyperglycinemia Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jun 22, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 09, 2022 | This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 401 of the AMT protein (p.Thr401Asn). This variant is present in population databases (rs752952950, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with AMT-related conditions. ClinVar contains an entry for this variant (Variation ID: 1052844). 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) performed at Invitae indicates that this missense variant is not expected to disrupt AMT protein function. 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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at