X-138710999-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM2 PP5

The NM_004114.5(FGF13):c.5C>G(p.Ala2Gly) 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 Likely pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 25)
• Consequence: FGF13 NM_004114.5 missense
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.12

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]

ACMG classification

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-138710999-G-C is Pathogenic according to our data. Variant chrX-138710999-G-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1809807.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF13	NM_004114.5	c.5C>G	p.Ala2Gly	missense_variant	1/5	ENST00000315930.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF13	ENST00000315930.11	c.5C>G	p.Ala2Gly	missense_variant	1/5	1	NM_004114.5	P4

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 25

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Developmental and epileptic encephalopathy, 90 Pathogenic:1

Likely pathogenic, no assertion criteria provided

clinical testing

Dept of Pediatric nervous, The Second Affiliated Hospital Zhejiang University School of Medicine

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
Cadd	Pathogenic	28
Dann	Uncertain	1.0
DEOGEN2	Benign	0.30	T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Pathogenic	0.75	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Uncertain	0.21	D
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	1.0	D;D;D;D;D
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.44
Sift	Uncertain	0.0070	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.43
MutPred		0.21		Gain of relative solvent accessibility (P = 0.09);
MVP		0.92
ClinPred		0.84	D
GERP RS		4.3
Varity_R		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-137793161;