X-54470714-TGG-TGGGGGGGGGGGGGGGAGGGGCTCCGGGGG

Position:

• chrX-54470714-TGG-TGGGGGGGGGGGGGGGAGGGGCTCCGGGGG

Variant summary

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

The ENST00000375135.4(FGD1):​c.527_528insCCCGGAGCCCCTCCCCCCCCCCCCCCC​(p.Pro176_Leu177insProGluProLeuProProProProPro) variant causes a 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. Synonymous variant affecting the same amino acid position (i.e. P176P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 19)
• Consequence: FGD1 ENST00000375135.4 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 ENST00000375135.4.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGD1	NM_004463.3	c.527_528insCCCGGAGCCCCTCCCCCCCCCCCCCCC	p.Pro176_Leu177insProGluProLeuProProProProPro	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_528insCCCGGAGCCCCTCCCCCCCCCCCCCCC	p.Pro176_Leu177insProGluProLeuProProProProPro	inframe_insertion	3/18	1	NM_004463.3	ENSP00000364277	P1

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Cov.: 16

GnomAD4 genome Cov.: 19

Alfa AF: 0.0000552 Hom.: 3

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

LitVar

Other links and lift over

dbSNP: rs756586058; hg19: chrX-54497147;