Variant X-138739247-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The ENST00000305414.9(FGF13):c.23A>G(p.Tyr8Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000595 in 1,125,283 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 170 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., 10 hem., cov: 23)

Exomes 𝑓: 0.00063 ( 0 hom. 160 hem. )

Consequence

FGF13
ENST00000305414.9 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.29

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21393716).

BP6

Variant X-138739247-T-C is Benign according to our data. Variant chrX-138739247-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3025497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 10 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons
FGF13	NM_033642.3 linkuse as main transcript	c.23A>G	p.Tyr8Cys	missense_variant	1/5
FGF13	NM_001139498.2 linkuse as main transcript	c.50-30319A>G		intron_variant
FGF13	NM_001139500.2 linkuse as main transcript	c.218-30319A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Appris	UniProt
FGF13	ENST00000305414.9 linkuse as main transcript	c.23A>G	p.Tyr8Cys	missense_variant	1/5	1		Q92913-2
FGF13	ENST00000436198.6 linkuse as main transcript	c.218-30319A>G		intron_variant		2	A1	Q92913-3
FGF13	ENST00000441825.8 linkuse as main transcript	c.131-30319A>G		intron_variant		5		Q92913-5

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

112201

Hom.:

Cov.:

AF XY:

0.000291

AC XY:

AN XY:

34363

show subpopulations

Gnomad AFR

AF:

0.000259

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000432

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000370

AC:

AN:

175674

Hom.:

AF XY:

0.000311

AC XY:

AN XY:

61040

show subpopulations

Gnomad AFR exome

AF:

0.000238

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000126

Gnomad NFE exome

AF:

0.000759

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000631

AC:

639

AN:

1013082

Hom.:

Cov.:

AF XY:

0.000525

AC XY:

160

AN XY:

304964

show subpopulations

Gnomad4 AFR exome

AF:

0.0000407

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000534

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000223

Gnomad4 NFE exome

AF:

0.000803

Gnomad4 OTH exome

AF:

0.000279

GnomAD4 genome

AF:

0.000276

AC:

AN:

112201

Hom.:

Cov.:

AF XY:

0.000291

AC XY:

AN XY:

34363

show subpopulations

Gnomad4 AFR

AF:

0.000259

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000432

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000452

Hom.:

Bravo

AF:

0.000238

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00138

AC:

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.000446

AC:

ExAC

AF:

0.000552

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

FGF13-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 08, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

FGF13: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.96

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.48

M_CAP

Pathogenic

0.36

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.58

MutationTaster

Benign

1.0

D;D;D;N

PROVEAN

Benign

-0.070

REVEL

Benign

0.24

Sift

Benign

0.18

Sift4G

Benign

0.18

Polyphen

0.017

Vest4

0.58

MVP

0.91

ClinPred

0.055

GERP RS

6.0

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over