rs398122957
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001291303.3(FAT4):c.11461C>T(p.Arg3821Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,672 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 Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001291303.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FAT4 | NM_001291303.3 | c.11461C>T | p.Arg3821Ter | stop_gained | 10/18 | ENST00000394329.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FAT4 | ENST00000394329.9 | c.11461C>T | p.Arg3821Ter | stop_gained | 10/18 | 5 | NM_001291303.3 | P1 | |
FAT4 | ENST00000335110.5 | c.6349C>T | p.Arg2117Ter | stop_gained | 9/15 | 1 | |||
FAT4 | ENST00000674496.2 | c.6232C>T | p.Arg2078Ter | stop_gained | 9/17 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461672Hom.: 0 Cov.: 73 AF XY: 0.00000138 AC XY: 1AN XY: 727162
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Van Maldergem syndrome 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 2013 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 19, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 89009). This premature translational stop signal has been observed in individual(s) with Van Maldergem syndrome (VMS) (PMID: 24056717). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg3819*) in the FAT4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FAT4 are known to be pathogenic (PMID: 24056717, 24913602). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at