4-186588684-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005245.4(FAT1):c.13675G>A(p.Val4559Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000291 in 1,613,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_005245.4 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FAT1 | NM_005245.4 | c.13675G>A | p.Val4559Ile | missense_variant | Exon 27 of 27 | ENST00000441802.7 | NP_005236.2 | |
FAT1 | XM_005262834.4 | c.13711G>A | p.Val4571Ile | missense_variant | Exon 28 of 28 | XP_005262891.1 | ||
FAT1 | XM_005262835.3 | c.13711G>A | p.Val4571Ile | missense_variant | Exon 28 of 28 | XP_005262892.1 | ||
FAT1 | XM_006714139.4 | c.13675G>A | p.Val4559Ile | missense_variant | Exon 27 of 27 | XP_006714202.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FAT1 | ENST00000441802.7 | c.13675G>A | p.Val4559Ile | missense_variant | Exon 27 of 27 | 5 | NM_005245.4 | ENSP00000406229.2 | ||
FAT1 | ENST00000512772.5 | c.1012G>A | p.Val338Ile | missense_variant | Exon 4 of 4 | 2 | ENSP00000424157.1 | |||
FAT1 | ENST00000500085.2 | n.1367G>A | non_coding_transcript_exon_variant | Exon 3 of 3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152146Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000281 AC: 7AN: 249134Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 135154
GnomAD4 exome AF: 0.0000253 AC: 37AN: 1461710Hom.: 0 Cov.: 31 AF XY: 0.0000275 AC XY: 20AN XY: 727136
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152264Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74466
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.13675G>A (p.V4559I) alteration is located in exon 27 (coding exon 26) of the FAT1 gene. This alteration results from a G to A substitution at nucleotide position 13675, causing the valine (V) at amino acid position 4559 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
This variant is present in population databases (rs146328457, gnomAD 0.009%). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 4559 of the FAT1 protein (p.Val4559Ile). This variant has not been reported in the literature in individuals affected with FAT1-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at