Variant X-138632900-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004114.5(FGF13):c.688T>C(p.Ser230Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 1,208,553 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 46 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., 7 hem., cov: 23)

Exomes 𝑓: 0.000098 ( 0 hom. 39 hem. )

Consequence

FGF13
NM_004114.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 8.95

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03316778).

BP6

Variant X-138632900-A-G is Benign according to our data. Variant chrX-138632900-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 741299.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-138632900-A-G is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 7 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF13	NM_004114.5 linkuse as main transcript	c.688T>C	p.Ser230Pro	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.688T>C	p.Ser230Pro	missense_variant	5/5	1	NM_004114.5	ENSP00000322390.6		Q92913-1

Frequencies

GnomAD3 genomes

AF:

0.000126

AC:

AN:

110922

Hom.:

Cov.:

AF XY:

0.000211

AC XY:

AN XY:

33122

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00417

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000378

Gnomad OTH

AF:

0.000672

GnomAD3 exomes

AF:

0.000218

AC:

AN:

183248

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

67682

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000219

Gnomad ASJ exome

AF:

0.00454

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000984

AC:

108

AN:

1097631

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

363011

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000142

Gnomad4 ASJ exome

AF:

0.00413

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000166

Gnomad4 OTH exome

AF:

0.000195

GnomAD4 genome

AF:

0.000126

AC:

AN:

110922

Hom.:

Cov.:

AF XY:

0.000211

AC XY:

AN XY:

33122

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00417

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000378

Gnomad4 OTH

AF:

0.000672

Alfa

AF:

0.000651

Hom.:

Bravo

AF:

0.000166

ExAC

AF:

0.000165

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Uncertain

0.033

BayesDel_noAF

Uncertain

0.080

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;.;.;.;.

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.86

D;D;D;D;D

M_CAP

Pathogenic

0.65

MetaRNN

Benign

0.033

T;T;T;T;T

MetaSVM

Benign

-0.38

MutationAssessor

Benign

0.82

L;.;.;.;.

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.32

N;N;N;.;.

REVEL

Uncertain

0.37

Sift

Benign

0.14

T;T;T;.;.

Sift4G

Benign

0.13

T;T;T;T;T

Polyphen

0.013

B;P;.;.;.

Vest4

0.62

MVP

0.93

ClinPred

0.11

GERP RS

5.8

Varity_R

0.41

gMVP

0.82

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

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