X-54470714-TGG-TGGGGGGGGGAGGGGCCCCAGGGG

Position:

• chrX-54470714-TGG-TGGGGGGGGGAGGGGCCCCAGGGG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM4

The NM_004463.3(FGD1):​c.527_528insCCTGGGGCCCCTCCCCCCCCC​(p.Pro176_Leu177insLeuGlyProLeuProProPro) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 19)
  • Exomes 𝑓: 0.0000056 (0 hom. 0 hem.)
• Consequence: FGD1 NM_004463.3 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.452

Genes affected

FGD1 (HGNC:3663): (FYVE, RhoGEF and PH domain containing 1) This gene encodes a protein that contains Dbl (DH) and pleckstrin (PH) homology domains and is similar to the Rho family of small GTP-binding proteins. The encoded protein specifically binds to the Rho family GTPase Cdc42Hs and can stimulate the GDP-GTP exchange of the isoprenylated form of Cdc42Hs. It also stimulates the mitogen activated protein kinase cascade leading to c-Jun kinase SAPK/JNK1 activation. Defects in this gene are the cause of the faciogenital dysplasia in Aarskog-Scott syndrome and a syndromatic form of X-linked cognitive disability. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_004463.3.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGD1	NM_004463.3	c.527_528insCCTGGGGCCCCTCCCCCCCCC	p.Pro176_Leu177insLeuGlyProLeuProProPro	disruptive_inframe_insertion	3/18	ENST00000375135.4	NP_004454.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGD1	ENST00000375135.4	c.527_528insCCTGGGGCCCCTCCCCCCCCC	p.Pro176_Leu177insLeuGlyProLeuProProPro	disruptive_inframe_insertion	3/18	1	NM_004463.3	ENSP00000364277.3

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome AF: 0.00000556 AC: 1 AN: 179912 Hom.: 0 Cov.: 16 AF XY: 0.00 AC XY: 0 AN XY: 37590

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000840

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 19

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-54497147;