X-11294791-G-A
Variant names:
Variant summary
Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_001142.2(AMELX):c.3G>A(p.Met1?) variant causes a start lost change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 23)
Consequence
AMELX
NM_001142.2 start_lost
NM_001142.2 start_lost
Scores
6
5
2
Clinical Significance
Conservation
PhyloP100: 5.03
Publications
0 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]
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ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 8 ACMG points.
PVS1
Start lost variant, next in-frame start position is after 6 pathogenic variants. Next in-frame start position is after 17 codons. Genomic position: 11294837. Lost 0.085 part of the original CDS.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant X-11294791-G-A is Pathogenic according to our data. Variant chrX-11294791-G-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 3598004.Status of the report is criteria_provided_single_submitter, 1 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
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| AMELX | TSL:1 MANE Select | c.3G>A | p.Met1? | start_lost | Exon 2 of 6 | ENSP00000370090.3 | Q99217-1 | ||
| AMELX | TSL:1 | c.3G>A | p.Met1? | start_lost | Exon 2 of 7 | ENSP00000370088.3 | Q99217-3 | ||
| ARHGAP6 | TSL:1 MANE Select | c.589-40084C>T | intron | N/A | ENSP00000338967.4 | O43182-1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
23
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome
GnomAD4 genome
Cov.:
23
ClinVar
ClinVar submissions
View on ClinVar Significance:Likely pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Amelogenesis imperfecta type 1E (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
T
PhyloP100
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
P
Vest4
MutPred
Gain of catalytic residue at M1 (P = 0.0237)
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: -14
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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