rs398123024
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_003867.4(FGF17):c.323T>C(p.Ile108Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).
Frequency
Genomes: not found (cov: 33)
Consequence
FGF17
NM_003867.4 missense
NM_003867.4 missense
Scores
9
7
1
Clinical Significance
Conservation
PhyloP100: 8.02
Genes affected
FGF17 (HGNC:3673): (fibroblast growth factor 17) This gene encodes a member of the fibroblast growth factor (FGF) family. Member of the FGF family 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 protein is expressed during embryogenesis and in the adult cerebellum and cortex and may be essential for vascular growth and normal brain development. Mutations in this gene are the cause of hypogonadotropic hypogonadism 20 with or without anosmia. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.952
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FGF17 | NM_003867.4 | c.323T>C | p.Ile108Thr | missense_variant | 4/5 | ENST00000359441.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FGF17 | ENST00000359441.4 | c.323T>C | p.Ile108Thr | missense_variant | 4/5 | 1 | NM_003867.4 | P4 | |
FGF17 | ENST00000518533.5 | c.290T>C | p.Ile97Thr | missense_variant | 4/5 | 1 | A1 | ||
FGF17 | ENST00000524314.1 | n.1693T>C | non_coding_transcript_exon_variant | 2/3 | 2 | ||||
FGF17 | ENST00000521709.1 | n.595+308T>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: risk factor
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hypogonadotropic hypogonadism 20 with or without anosmia Other:1
risk factor, no assertion criteria provided | literature only | OMIM | May 02, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MutPred
0.80
.;Gain of disorder (P = 0.021);
MVP
MPC
2.5
ClinPred
D
GERP RS
Varity_R
gMVP
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