rs10521792

Positions:

• chrX-139035247-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001139500.2(FGF13):​c.49+168812T>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 NM_001139500.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.949

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
FGF13	NM_001139500.2	c.49+168812T>C		intron_variant			NP_001132972.1
FGF13	NM_001139501.2	c.-148-44630T>C		intron_variant			NP_001132973.1
FGF13	NM_001139498.2	c.49+168812T>C		intron_variant			NP_001132970.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.161 AC: 17890 AN: 110977 Hom.: 1274 Cov.: 23 AF XY: 0.153 AC XY: 5088 AN XY: 33311

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

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.0762

Gnomad4 EAS AF: 0.0729

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.153

Alfa AF: 0.134 Hom.: 2400

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10521792; hg19: chrX-138117409;