rs199682210
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP3_ModerateBS1_Supporting
The NM_001291303.3(FAT4):c.12851C>T(p.Ser4284Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00019 in 1,613,238 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. S4284S) has been classified as Benign.
Frequency
Consequence
NM_001291303.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FAT4 | NM_001291303.3 | c.12851C>T | p.Ser4284Phe | missense_variant | 17/18 | ENST00000394329.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FAT4 | ENST00000394329.9 | c.12851C>T | p.Ser4284Phe | missense_variant | 17/18 | 5 | NM_001291303.3 | P1 | |
FAT4 | ENST00000335110.5 | c.7568C>T | p.Ser2523Phe | missense_variant | 14/15 | 1 | |||
FAT4 | ENST00000674496.2 | c.7622C>T | p.Ser2541Phe | missense_variant | 16/17 |
Frequencies
GnomAD3 genomes ? AF: 0.000118 AC: 18AN: 152108Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000998 AC: 25AN: 250418Hom.: 0 AF XY: 0.000111 AC XY: 15AN XY: 135544
GnomAD4 exome AF: 0.000198 AC: 289AN: 1461130Hom.: 0 Cov.: 31 AF XY: 0.000194 AC XY: 141AN XY: 726818
GnomAD4 genome ? AF: 0.000118 AC: 18AN: 152108Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74290
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 21, 2022 | This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 4282 of the FAT4 protein (p.Ser4282Phe). This variant is present in population databases (rs199682210, gnomAD 0.02%). This missense change has been observed in individual(s) with Hennekam lymphangiectasia–lymphedema syndrome (PMID: 24913602). This variant is also known as c.12851C>T, p.Ser4284Phe. ClinVar contains an entry for this variant (Variation ID: 156111). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 09, 2017 | - - |
Hennekam lymphangiectasia-lymphedema syndrome 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 2014 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at