rs1554109707
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM2PM5PP3_StrongPP5_Moderate
The NM_182925.5(FLT4):c.3391G>C(p.Gly1131Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1131S) has been classified as Likely pathogenic.
Frequency
Consequence
NM_182925.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLT4 | NM_182925.5 | c.3391G>C | p.Gly1131Arg | missense_variant | 25/30 | ENST00000261937.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLT4 | ENST00000261937.11 | c.3391G>C | p.Gly1131Arg | missense_variant | 25/30 | 1 | NM_182925.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248558Hom.: 0 AF XY: 0.00000743 AC XY: 1AN XY: 134546
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:3
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Feb 21, 2022 | Observed in multiple unrelated patients with congenital lymphedema referred for genetic testing at GeneDx and in the published literature (Connell et al., 2009; Gordon et al., 2013); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 19002718, 10835628, 11114740, 24167460, 23074044) - |
Pathogenic, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Pathogenic, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at