X-11298243-C-T
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The NM_001142.2(AMELX):c.110C>T(p.Thr37Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,727 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 23)
Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )
Consequence
AMELX
NM_001142.2 missense
NM_001142.2 missense
Scores
8
7
2
Clinical Significance
Conservation
PhyloP100: 2.71
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 made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.949
PP5
Variant X-11298243-C-T is Pathogenic according to our data. Variant chrX-11298243-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 11140.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.110C>T | p.Thr37Ile | missense_variant | 4/6 | ENST00000380714.7 | |
ARHGAP6 | NM_013427.3 | c.589-43536G>A | intron_variant | ENST00000337414.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AMELX | ENST00000380714.7 | c.110C>T | p.Thr37Ile | missense_variant | 4/6 | 1 | NM_001142.2 | P1 | |
ARHGAP6 | ENST00000337414.9 | c.589-43536G>A | intron_variant | 1 | NM_013427.3 | P2 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 genomes
Cov.:
23
GnomAD4 exome AF: 9.11e-7 AC: 1AN: 1097727Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 1AN XY: 363123
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GnomAD4 genome Cov.: 23
GnomAD4 genome
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23
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Amelogenesis imperfecta type 1E Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 01, 2002 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Uncertain
DEOGEN2
Pathogenic
.;D;.
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
.;M;.
MutationTaster
Benign
A;A;A;A;A;A;A;A
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;T;D
Sift4G
Benign
T;D;T
Polyphen
D;D;D
Vest4
MutPred
0.69
.;Loss of sheet (P = 0.0357);.;
MVP
MPC
0.88
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at