rs387906488

Variant names:

• chrX-11294801-ATTTTATTTG-A
• rs387906488
• NM_001142.2:c.14_22delTTTTATTTG

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PM4 PP5

The NM_001142.2(AMELX):​c.14_22delTTTTATTTG​(p.Ile5_Ala8delinsThr) variant causes a disruptive 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 disruptive_inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.05
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 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 VariationId is 11138.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMELX	NM_001142.2	MANE Select	c.14_22delTTTTATTTG	p.Ile5_Ala8delinsThr	disruptive_inframe_deletion	Exon 2 of 6	NP_001133.1	Q99217-1
	ARHGAP6	NM_013427.3	MANE Select	c.589-40103_589-40095delCAAATAAAA		intron	N/A	NP_038286.2	O43182-1
	AMELX	NM_182680.1		c.14_22delTTTTATTTG	p.Ile5_Ala8delinsThr	disruptive_inframe_deletion	Exon 2 of 7	NP_872621.1	Q99217-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMELX	ENST00000380714.7	TSL:1 MANE Select	c.14_22delTTTTATTTG	p.Ile5_Ala8delinsThr	disruptive_inframe_deletion	Exon 2 of 6	ENSP00000370090.3	Q99217-1
	AMELX	ENST00000380712.7	TSL:1	c.14_22delTTTTATTTG	p.Ile5_Ala8delinsThr	disruptive_inframe_deletion	Exon 2 of 7	ENSP00000370088.3	Q99217-3
	ARHGAP6	ENST00000337414.9	TSL:1 MANE Select	c.589-40103_589-40095delCAAATAAAA		intron	N/A	ENSP00000338967.4	O43182-1

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

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Amelogenesis imperfecta type 1E (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.1
Mutation Taster		=1/199	disease causing (ClinVar)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs387906488;

hg19: chrX-11312921;