11-69818784-G-T
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PM2
The NM_005247.4(FGF3):c.150C>A(p.Cys50*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000744 in 1,343,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as not provided (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 7.4e-7 ( 0 hom. )
Consequence
FGF3
NM_005247.4 stop_gained
NM_005247.4 stop_gained
Scores
2
4
Clinical Significance
Conservation
PhyloP100: 2.47
Publications
3 publications found
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]
FGF3 Gene-Disease associations (from GenCC):
- deafness with labyrinthine aplasia, microtia, and microdontiaInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 10 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_005247.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| FGF3 | NM_005247.4 | MANE Select | c.150C>A | p.Cys50* | stop_gained | Exon 1 of 3 | NP_005238.1 | P11487 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| FGF3 | ENST00000334134.4 | TSL:1 MANE Select | c.150C>A | p.Cys50* | stop_gained | Exon 1 of 3 | ENSP00000334122.2 | P11487 | |
| ENSG00000300527 | ENST00000772585.1 | n.-187G>T | upstream_gene | N/A |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 7.44e-7 AC: 1AN: 1343576Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 663178 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
1343576
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
663178
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
27342
American (AMR)
AF:
AC:
0
AN:
30716
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
23702
East Asian (EAS)
AF:
AC:
0
AN:
30806
South Asian (SAS)
AF:
AC:
0
AN:
75236
European-Finnish (FIN)
AF:
AC:
0
AN:
34196
Middle Eastern (MID)
AF:
AC:
0
AN:
4434
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1061388
Other (OTH)
AF:
AC:
0
AN:
55756
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:not provided
Revision:no classification provided
Pathogenic
VUS
Benign
Condition
-
-
-
Deafness with labyrinthine aplasia, microtia, and microdontia (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
PhyloP100
Vest4
GERP RS
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
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.