Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000481.4(AMT):c.101G>T(p.Arg34Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R34H) has been classified as Likely benign.
AMT (HGNC:473): (aminomethyltransferase) This gene encodes one of four critical components of the glycine cleavage system. Mutations in this gene have been associated with glycine encephalopathy. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (MetaRNN=0.24422911).
Gain of catalytic residue at R34 (P = 0.0405);Gain of catalytic residue at R34 (P = 0.0405);Gain of catalytic residue at R34 (P = 0.0405);Gain of catalytic residue at R34 (P = 0.0405);Gain of catalytic residue at R34 (P = 0.0405);Gain of catalytic residue at R34 (P = 0.0405);Gain of catalytic residue at R34 (P = 0.0405);Gain of catalytic residue at R34 (P = 0.0405);