rs774047997
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000142.5(FGFR3):c.916G>A(p.Val306Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,459,794 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. V306V) has been classified as Likely benign.
Frequency
Consequence
NM_000142.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FGFR3 | NM_000142.5 | c.916G>A | p.Val306Ile | missense_variant | 7/18 | ENST00000440486.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FGFR3 | ENST00000440486.8 | c.916G>A | p.Val306Ile | missense_variant | 7/18 | 5 | NM_000142.5 | P4 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD3 exomes AF: 0.0000448 AC: 11AN: 245456Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 133916
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1459794Hom.: 0 Cov.: 37 AF XY: 0.00000551 AC XY: 4AN XY: 726198
GnomAD4 genome Cov.: 34
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 25, 2022 | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 306 of the FGFR3 protein (p.Val306Ile). This variant is present in population databases (rs774047997, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with FGFR3-related conditions. ClinVar contains an entry for this variant (Variation ID: 582777). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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