Variant X-138632869-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004114.5(FGF13):c.719G>A(p.Ser240Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,096,310 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

FGF13
NM_004114.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57

Variant links:

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]

FGF13 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF13	NM_004114.5 linkuse as main transcript	c.719G>A	p.Ser240Asn	missense_variant	5/5	ENST00000315930.11	NP_004105.1	Q92913-1A8K1P5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF13	ENST00000315930.11 linkuse as main transcript	c.719G>A	p.Ser240Asn	missense_variant	5/5	1	NM_004114.5	ENSP00000322390.6		Q92913-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.12e-7

AC:

AN:

1096310

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

361808

show subpopulations

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:

0.00000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jun 24, 2024

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.21

T;.;.;.;.

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.82

T;T;T;T;T

M_CAP

Pathogenic

0.77

MetaRNN

Uncertain

0.54

D;D;D;D;D

MetaSVM

Benign

-0.71

MutationAssessor

Benign

0.81

L;.;.;.;.

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.43

N;N;N;.;.

REVEL

Uncertain

0.36

Sift

Benign

1.0

T;T;T;.;.

Sift4G

Benign

0.57

T;T;T;T;T

Polyphen

0.0010

B;B;.;.;.

Vest4

0.51

MutPred

0.056

Loss of phosphorylation at S240 (P = 0.021);.;.;.;.;

MVP

0.74

ClinPred

0.83

GERP RS

5.9

Varity_R

0.39

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over