X-138649185-T-C

Variant names:

• chrX-138649185-T-C
• rs2267628
• NM_004114.5:c.403-13530A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004114.5(FGF13):​c.403-13530A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.68 (19023 hom., 22033 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: FGF13 NM_004114.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289
• Publications: 4 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF13	NM_004114.5	c.403-13530A>G		intron_variant	Intron 3 of 4	ENST00000315930.11	NP_004105.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF13	ENST00000315930.11	c.403-13530A>G		intron_variant	Intron 3 of 4	1	NM_004114.5	ENSP00000322390.6

Frequencies

GnomAD3 genomes AF: 0.677 AC: 74770 AN: 110466 Hom.: 19018 Cov.: 23

Gnomad AFR AF: 0.914

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.654

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.677 AC: 74832 AN: 110518 Hom.: 19023 Cov.: 23 AF XY: 0.673 AC XY: 22033 AN XY: 32750

African (AFR) AF: 0.914 AC: 27818 AN: 30421

American (AMR) AF: 0.689 AC: 7165 AN: 10398

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 1550 AN: 2631

East Asian (EAS) AF: 0.905 AC: 3150 AN: 3482

South Asian (SAS) AF: 0.708 AC: 1848 AN: 2610

European-Finnish (FIN) AF: 0.576 AC: 3369 AN: 5854

Middle Eastern (MID) AF: 0.605 AC: 127 AN: 210

European-Non Finnish (NFE) AF: 0.538 AC: 28385 AN: 52746

Other (OTH) AF: 0.655 AC: 983 AN: 1500

Alfa AF: 0.612 Hom.: 10237

Bravo AF: 0.694

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.86
DANN	Benign	0.69
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2267628; hg19: chrX-137731346;