rs199702395
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PM5
The NM_000142.5(FGFR3):c.1031C>T(p.Ser344Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,614,084 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S344C) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000142.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FGFR3 | NM_000142.5 | c.1031C>T | p.Ser344Phe | missense_variant | 8/18 | ENST00000440486.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FGFR3 | ENST00000440486.8 | c.1031C>T | p.Ser344Phe | missense_variant | 8/18 | 5 | NM_000142.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152232Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250930Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135860
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461734Hom.: 0 Cov.: 33 AF XY: 0.0000110 AC XY: 8AN XY: 727176
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152350Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74508
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 22, 2022 | This variant has not been reported in the literature in individuals affected with FGFR3-related conditions. This variant is present in population databases (rs199702395, gnomAD 0.002%). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 344 of the FGFR3 protein (p.Ser344Phe). ClinVar contains an entry for this variant (Variation ID: 134402). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at