X-139035247-A-G

Variant names:

• chrX-139035247-A-G
• rs10521792
• ENST00000421460.1:c.-113+168169T>C

Variant summary

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

The ENST00000421460.1(FGF13):​c.-113+168169T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 111,025 control chromosomes in the GnomAD database, including 1,278 homozygotes. There are 5,107 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 0.16 (1278 hom., 5107 hem., cov: 23)
• Consequence: FGF13 ENST00000421460.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.949
• Publications: 2 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, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF13	NM_001139500.2	c.49+168812T>C		intron_variant	Intron 2 of 6		NP_001132972.1
FGF13	NM_001139501.2	c.-148-44630T>C		intron_variant	Intron 2 of 7		NP_001132973.1
FGF13	NM_001139498.2	c.49+168812T>C		intron_variant	Intron 2 of 5		NP_001132970.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF13	ENST00000421460.1	c.-113+168169T>C		intron_variant	Intron 1 of 2	1		ENSP00000388688.1
FGF13	ENST00000436198.6	c.49+168812T>C		intron_variant	Intron 2 of 6	2		ENSP00000396198.2
FGF13	ENST00000441825.8	c.-148-44630T>C		intron_variant	Intron 1 of 6	5		ENSP00000409276.2

Frequencies

GnomAD3 genomes AF: 0.161 AC: 17890 AN: 110977 Hom.: 1274 Cov.: 23

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.0146

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.0762

Gnomad EAS AF: 0.0732

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.161 AC: 17927 AN: 111025 Hom.: 1278 Cov.: 23 AF XY: 0.153 AC XY: 5107 AN XY: 33369

African (AFR) AF: 0.276 AC: 8432 AN: 30499

American (AMR) AF: 0.172 AC: 1803 AN: 10474

Ashkenazi Jewish (ASJ) AF: 0.0762 AC: 201 AN: 2638

East Asian (EAS) AF: 0.0729 AC: 255 AN: 3496

South Asian (SAS) AF: 0.192 AC: 511 AN: 2657

European-Finnish (FIN) AF: 0.109 AC: 651 AN: 5990

Middle Eastern (MID) AF: 0.153 AC: 33 AN: 216

European-Non Finnish (NFE) AF: 0.110 AC: 5800 AN: 52862

Other (OTH) AF: 0.153 AC: 231 AN: 1508

Alfa AF: 0.160 Hom.: 5057

Bravo AF: 0.178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.069
DANN	Benign	0.67
PhyloP100		-0.95
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: rs10521792; hg19: chrX-138117409;