chr3-192144106-G-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_004113.6(FGF12):c.449C>T(p.Ser150Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,612,456 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 Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S150S) has been classified as Likely benign.
Frequency
Consequence
NM_004113.6 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FGF12 | NM_004113.6 | c.449C>T | p.Ser150Leu | missense_variant | 6/6 | ENST00000445105.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FGF12 | ENST00000445105.7 | c.449C>T | p.Ser150Leu | missense_variant | 6/6 | 1 | NM_004113.6 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000658 AC: 10AN: 152076Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251166Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135752
GnomAD4 exome AF: 0.00000685 AC: 10AN: 1460262Hom.: 0 Cov.: 29 AF XY: 0.00000275 AC XY: 2AN XY: 726556
GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152194Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74408
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 20, 2023 | ClinVar contains an entry for this variant (Variation ID: 1355797). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 212 of the FGF12 protein (p.Ser212Leu). This variant is present in population databases (rs368025154, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with FGF12-related conditions. 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 FGF12 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