17-76733165-TACC-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4_SupportingPP5
The NM_001080510.5(METTL23):c.278_280delCAC(p.Pro93del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,613,966 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001080510.5 disruptive_inframe_deletion
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
METTL23 | NM_001080510.5 | c.278_280delCAC | p.Pro93del | disruptive_inframe_deletion | Exon 3 of 5 | ENST00000341249.11 | NP_001073979.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
METTL23 | ENST00000341249.11 | c.278_280delCAC | p.Pro93del | disruptive_inframe_deletion | Exon 3 of 5 | 1 | NM_001080510.5 | ENSP00000341543.5 | ||
ENSG00000267168 | ENST00000587459.1 | c.194_196delCAC | p.Pro65del | disruptive_inframe_deletion | Exon 1 of 2 | 5 | ENSP00000466829.1 |
Frequencies
GnomAD3 genomes AF: 0.000131 AC: 20AN: 152244Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000100 AC: 25AN: 248960Hom.: 0 AF XY: 0.0000962 AC XY: 13AN XY: 135076
GnomAD4 exome AF: 0.000156 AC: 228AN: 1461604Hom.: 0 AF XY: 0.000166 AC XY: 121AN XY: 727062
GnomAD4 genome AF: 0.000131 AC: 20AN: 152362Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74510
ClinVar
Submissions by phenotype
not provided Pathogenic:1Uncertain:1
In-frame deletion of 1 amino acid(s) in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
- -
Inborn genetic diseases Uncertain:1
The c.278_280delCAC (p.P93del) alteration, located in exon 3 (coding exon 2) of the METTL23 gene, results from an in-frame deletion at nucleotide positions c.278 to c.280. This results in the deletion of a proline residue at codon 93. Based on data from gnomAD, this allele has an overall frequency of 0.010% (28/280370) total alleles studied. The highest observed frequency was 0.025% (6/24172) of African alleles. This amino acid position is not well conserved in available vertebrate species. The p.P93 amino acid is located in the lysine methyltransferase domain of the METTL23 protein. Methyltransferases catalyze the transfer of a methyl group from S-adenosyl L-methionine (SAM) to a nucleophilic acceptor (Kozbial, 2005). All methyltransferases share a conserved region of approximately 130 amino acids, which allows them to bind to SAM (Schluckebier, 1995). This alteration is predicted to be deleterious by in silico analysis (Choi, 2012). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Intellectual disability, autosomal recessive 44 Uncertain:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at