rs281860304
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPM2
The NM_005247.4(FGF3):c.394del(p.Arg132GlyfsTer26) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars).
Frequency
Genomes: not found (cov: 33)
Consequence
FGF3
NM_005247.4 frameshift
NM_005247.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.34
Genes affected
FGF3 (HGNC:3681): (fibroblast growth factor 3) The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities and are involved in a variety of biological processes including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This gene was identified by its similarity with mouse fgf3/int-2, a proto-oncogene activated in virally induced mammary tumors in the mouse. Frequent amplification of this gene has been found in human tumors, which may be important for neoplastic transformation and tumor progression. Studies of the similar genes in mouse and chicken suggested the role in inner ear formation. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.453 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| FGF3 | NM_005247.4 | c.394del | p.Arg132GlyfsTer26 | frameshift_variant | 3/3 | ENST00000334134.4 | NP_005238.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| FGF3 | ENST00000334134.4 | c.394del | p.Arg132GlyfsTer26 | frameshift_variant | 3/3 | 1 | NM_005247.4 | ENSP00000334122 | P1 | |
| FGF3 | ENST00000646078.1 | n.241del | non_coding_transcript_exon_variant | 3/3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link
Submissions by phenotype
Deafness with labyrinthine aplasia, microtia, and microdontia Other:1
| not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at