14-24506587-A-G
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001308083.2(CMA1):c.-107T>C variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000992 in 1,613,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001308083.2 5_prime_UTR_premature_start_codon_gain
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CMA1 | NM_001836.5 | c.227T>C | p.Leu76Pro | missense_variant | Exon 3 of 5 | ENST00000250378.7 | NP_001827.1 | |
CMA1 | NM_001308083.2 | c.-107T>C | 5_prime_UTR_premature_start_codon_gain_variant | Exon 2 of 4 | NP_001295012.1 | |||
CMA1 | NM_001308083.2 | c.-107T>C | 5_prime_UTR_variant | Exon 2 of 4 | NP_001295012.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CMA1 | ENST00000206446.4 | c.-107T>C | 5_prime_UTR_premature_start_codon_gain_variant | Exon 2 of 4 | 1 | ENSP00000206446.4 | ||||
CMA1 | ENST00000250378.7 | c.227T>C | p.Leu76Pro | missense_variant | Exon 3 of 5 | 1 | NM_001836.5 | ENSP00000250378.3 | ||
CMA1 | ENST00000206446.4 | c.-107T>C | 5_prime_UTR_variant | Exon 2 of 4 | 1 | ENSP00000206446.4 | ||||
ENSG00000258744 | ENST00000555109.1 | n.144-1547A>G | intron_variant | Intron 1 of 1 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152158Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 251024Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135652
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461108Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5AN XY: 726866
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152158Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74336
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.227T>C (p.L76P) alteration is located in exon 3 (coding exon 3) of the CMA1 gene. This alteration results from a T to C substitution at nucleotide position 227, causing the leucine (L) at amino acid position 76 to be replaced by a proline (P). 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