rs387906488

chrX-11294801-ATTTTATTTG-A

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4 PP5

The NM_001142.2(AMELX):c.14_22del(p.Ile5_Ala8delinsThr) variant causes a inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 23)
• Consequence: AMELX NM_001142.2 inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.05

Genes affected

AMELX (HGNC:461): (amelogenin X-linked) This gene encodes a member of the amelogenin family of extracellular matrix proteins. Amelogenins are involved in biomineralization during tooth enamel development. Mutations in this gene cause X-linked amelogenesis imperfecta. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ARHGAP6 (HGNC:676): (Rho GTPase activating protein 6) This gene encodes a member of the rhoGAP family of proteins which play a role in the regulation of actin polymerization at the plasma membrane during several cellular processes. This protein is thought to have two independent functions, one as a GTPase-activating protein with specificity for RhoA, and another as a cytoskeletal protein that promotes actin remodeling. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001142.2.
• PP5: Variant X-11294801-ATTTTATTTG-A is Pathogenic according to our data. Variant chrX-11294801-ATTTTATTTG-A is described in ClinVar as [Pathogenic]. Clinvar id is 11138.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMELX	NM_001142.2	c.14_22del	p.Ile5_Ala8delinsThr	inframe_deletion	2/6	ENST00000380714.7
ARHGAP6	NM_013427.3	c.589-40103_589-40095del		intron_variant		ENST00000337414.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMELX	ENST00000380714.7	c.14_22del	p.Ile5_Ala8delinsThr	inframe_deletion	2/6	1	NM_001142.2	P1
ARHGAP6	ENST00000337414.9	c.589-40103_589-40095del		intron_variant		1	NM_013427.3	P2

Frequencies

GnomAD3 genomes Cov.: 23

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

GnomAD4 genome Cov.: 23

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Amelogenesis imperfecta type 1E Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 01, 1995

- -

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: rs387906488; hg19: chrX-11312921;