X-11298276-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001142.2(AMELX):c.143C>T(p.Pro48Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,207,719 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001142.2 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AMELX | NM_001142.2 | c.143C>T | p.Pro48Leu | missense_variant, splice_region_variant | Exon 4 of 6 | ENST00000380714.7 | NP_001133.1 | |
ARHGAP6 | NM_013427.3 | c.589-43569G>A | intron_variant | Intron 1 of 12 | ENST00000337414.9 | NP_038286.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AMELX | ENST00000380714.7 | c.143C>T | p.Pro48Leu | missense_variant, splice_region_variant | Exon 4 of 6 | 1 | NM_001142.2 | ENSP00000370090.3 | ||
ARHGAP6 | ENST00000337414.9 | c.589-43569G>A | intron_variant | Intron 1 of 12 | 1 | NM_013427.3 | ENSP00000338967.4 |
Frequencies
GnomAD3 genomes AF: 0.0000448 AC: 5AN: 111587Hom.: 0 Cov.: 23 AF XY: 0.0000887 AC XY: 3AN XY: 33807
GnomAD3 exomes AF: 0.0000327 AC: 6AN: 183416Hom.: 0 AF XY: 0.0000295 AC XY: 2AN XY: 67872
GnomAD4 exome AF: 0.0000128 AC: 14AN: 1096132Hom.: 0 Cov.: 31 AF XY: 0.00000830 AC XY: 3AN XY: 361574
GnomAD4 genome AF: 0.0000448 AC: 5AN: 111587Hom.: 0 Cov.: 23 AF XY: 0.0000887 AC XY: 3AN XY: 33807
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.185C>T (p.P62L) alteration is located in exon 5 (coding exon 4) of the AMELX gene. This alteration results from a C to T substitution at nucleotide position 185, causing the proline (P) at amino acid position 62 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at