X-138754725-C-A

Variant names:

• chrX-138754725-C-A
• rs591
• NM_001139500.2:c.218-45797G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001139500.2(FGF13):​c.218-45797G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 110,148 control chromosomes in the GnomAD database, including 6,372 homozygotes. There are 11,545 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (6372 hom., 11545 hem., cov: 22)
• Consequence: FGF13 NM_001139500.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 90

  Inheritance: XL Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001139500.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF13	NM_001139500.2		c.218-45797G>T		intron	N/A	NP_001132972.1	Q92913-3
	FGF13	NM_001139501.2		c.131-45797G>T		intron	N/A	NP_001132973.1	Q92913-5
	FGF13	NM_001139502.2		c.131-45797G>T		intron	N/A	NP_001132974.1	Q92913-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF13	ENST00000436198.6	TSL:2	c.218-45797G>T		intron	N/A	ENSP00000396198.2	Q92913-3
	FGF13	ENST00000441825.8	TSL:5	c.131-45797G>T		intron	N/A	ENSP00000409276.2	Q92913-5
	FGF13	ENST00000455663.5	TSL:3	c.236-45797G>T		intron	N/A	ENSP00000406916.1	B1AJW0

Frequencies

GnomAD3 genomes AF: 0.368 AC: 40534 AN: 110093 Hom.: 6367 Cov.: 22

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.305

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.332

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.368 AC: 40585 AN: 110148 Hom.: 6372 Cov.: 22 AF XY: 0.356 AC XY: 11545 AN XY: 32462

African (AFR) AF: 0.587 AC: 17728 AN: 30210

American (AMR) AF: 0.305 AC: 3145 AN: 10314

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 633 AN: 2637

East Asian (EAS) AF: 0.551 AC: 1897 AN: 3441

South Asian (SAS) AF: 0.356 AC: 912 AN: 2562

European-Finnish (FIN) AF: 0.303 AC: 1751 AN: 5772

Middle Eastern (MID) AF: 0.307 AC: 65 AN: 212

European-Non Finnish (NFE) AF: 0.259 AC: 13690 AN: 52835

Other (OTH) AF: 0.334 AC: 500 AN: 1499

Alfa AF: 0.325 Hom.: 2119

Bravo AF: 0.380

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.1
DANN	Benign	0.40
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs591; hg19: chrX-137836887;