Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_004169(SHMT1):c.1420C>T(p.Leu474Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 151908 control chromosomes in the gnomAD Genomes database, including 7394 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L474R) has been classified as Uncertain significance.
Verdict is Benign. Variant got -12 ACMG points.
GnomAD3 genomes AF: 0.305AC: 46364AN: 151908Hom.: 7394Cov.: 32 GnomAD3 exomes AF: 0.268AC: 58787AN: 219198Hom.: 8365 AF XY: 0.265AC XY: 31436AN XY: 118586 GnomAD4 exome AF: 0.300AC: 432575AN: 1442172Hom.: 67041 AF XY: 0.296AC XY: 211726AN XY: 715842
Submissions by phenotype
Gastrointestinal stromal tumor
|Uncertain significance, no assertion criteria provided||case-control||Department of Pharmacy and Biotechnology, University of Bologna||-||- -|
Find out detailed SpliceAI scores and Pangolin per-transcript scores at