chrX-138710963-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP5
The NM_004114.5(FGF13):c.41G>C(p.Arg14Thr) variant causes a missense 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 Pathogenic (no stars).
Frequency
Genomes: not found (cov: 25)
Consequence
FGF13
NM_004114.5 missense
NM_004114.5 missense
Scores
7
4
5
Clinical Significance
Conservation
PhyloP100: 7.36
Genes affected
FGF13 (HGNC:3670): (fibroblast growth factor 13) 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 is located in a region on chromosome X, which is associated with Borjeson-Forssman-Lehmann syndrome (BFLS), making it a possible candidate gene for familial cases of the BFLS, and for other syndromal and nonspecific forms of X-linked cognitive disability mapping to this region. Alternative splicing of this gene at the 5' end results in several transcript variants encoding different isoforms with different N-termini. [provided by RefSeq, Nov 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM1
?
In a region_of_interest Mediates targeting to the nucleus (size 61) in uniprot entity FGF13_HUMAN there are 6 pathogenic changes around while only 0 benign (100%) in NM_004114.5
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-138710963-C-G is Pathogenic according to our data. Variant chrX-138710963-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 997408.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-138710963-C-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FGF13 | NM_004114.5 | c.41G>C | p.Arg14Thr | missense_variant | 1/5 | ENST00000315930.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FGF13 | ENST00000315930.11 | c.41G>C | p.Arg14Thr | missense_variant | 1/5 | 1 | NM_004114.5 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 25
GnomAD3 genomes
?
Cov.:
25
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 25
GnomAD4 genome
?
Cov.:
25
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy, 90 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 19, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Benign
DEOGEN2
Benign
T
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L
MutationTaster
Benign
D;D;D;D;D
PROVEAN
Benign
N
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MutPred
Gain of phosphorylation at R14 (P = 0.0226);
MVP
ClinPred
D
GERP RS
Varity_R
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