rs370088878
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting
The NM_001291303.3(FAT4):c.9487G>A(p.Glu3163Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000384 in 1,613,926 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E3163Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_001291303.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FAT4 | NM_001291303.3 | c.9487G>A | p.Glu3163Lys | missense_variant | 10/18 | ENST00000394329.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FAT4 | ENST00000394329.9 | c.9487G>A | p.Glu3163Lys | missense_variant | 10/18 | 5 | NM_001291303.3 | P1 | |
FAT4 | ENST00000335110.5 | c.4375G>A | p.Glu1459Lys | missense_variant | 9/15 | 1 | |||
FAT4 | ENST00000674496.2 | c.4258G>A | p.Glu1420Lys | missense_variant | 9/17 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152116Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000319 AC: 8AN: 250656Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135452
GnomAD4 exome AF: 0.0000376 AC: 55AN: 1461810Hom.: 0 Cov.: 41 AF XY: 0.0000371 AC XY: 27AN XY: 727206
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152116Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74304
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 3161 of the FAT4 protein (p.Glu3161Lys). This variant is present in population databases (rs370088878, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with FAT4-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) performed at Invitae indicates that this missense variant is not expected to disrupt FAT4 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