rs281860307
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_005247.4(FGF3):c.457_458del(p.Trp153ValfsTer51) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,322 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
FGF3
NM_005247.4 frameshift
NM_005247.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.52
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 7 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. There are 5 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 11-69810566-CCA-C is Pathogenic according to our data. Variant chr11-69810566-CCA-C is described in ClinVar as [Pathogenic]. Clinvar id is 29818.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-69810566-CCA-C is described in Lovd as [Pathogenic]. Variant chr11-69810566-CCA-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FGF3 | NM_005247.4 | c.457_458del | p.Trp153ValfsTer51 | frameshift_variant | 3/3 | ENST00000334134.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FGF3 | ENST00000334134.4 | c.457_458del | p.Trp153ValfsTer51 | frameshift_variant | 3/3 | 1 | NM_005247.4 | P1 | |
FGF3 | ENST00000646078.1 | n.304_305del | non_coding_transcript_exon_variant | 3/3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460322Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 726356
GnomAD4 exome
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726356
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Deafness with labyrinthine aplasia, microtia, and microdontia Pathogenic:1Other:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 2011 | - - |
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at