X-138632868-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_004114.5(FGF13):c.720C>A(p.Ser240Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000639 in 1,096,056 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000064 (0 hom. 1 hem.)
• Consequence: FGF13 NM_004114.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.91

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 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF13	NM_004114.5	c.720C>A	p.Ser240Arg	missense_variant	5/5	ENST00000315930.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF13	ENST00000315930.11	c.720C>A	p.Ser240Arg	missense_variant	5/5	1	NM_004114.5	P4

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000639 AC: 7 AN: 1096056 Hom.: 0 Cov.: 30 AF XY: 0.00000277 AC XY: 1 AN XY: 361586

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000833

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jun 10, 2022

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
Cadd	Benign	22
Dann	Uncertain	0.98
DEOGEN2	Benign	0.24	T;.;.;.;.
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.89	D;D;D;D;D
M_CAP	Pathogenic	0.52	D
MetaRNN	Uncertain	0.52	D;D;D;D;D
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.4	L;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.59	N;N;N;.;.
REVEL	Uncertain	0.38
Sift	Benign	0.039	D;T;T;.;.
Sift4G	Benign	0.25	T;T;T;T;T
Polyphen		0.0010	B;B;.;.;.
Vest4		0.58
MutPred		0.29		Gain of MoRF binding (P = 2e-04);.;.;.;.;
MVP		0.99
ClinPred		0.27	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.47
gMVP		0.43

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-137715029;