12-53307490-T-TA
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_015665.6(AAAS):c.1639dupT(p.Ter547LeufsTer11) variant causes a frameshift, stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,611,106 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_015665.6 frameshift, stop_lost
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AAAS | NM_015665.6 | c.1639dupT | p.Ter547LeufsTer11 | frameshift_variant, stop_lost | Exon 16 of 16 | ENST00000209873.9 | NP_056480.1 | |
AAAS | NM_001173466.2 | c.1540dupT | p.Ter514LeufsTer11 | frameshift_variant, stop_lost | Exon 15 of 15 | NP_001166937.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152138Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1458968Hom.: 0 Cov.: 34 AF XY: 0.00000689 AC XY: 5AN XY: 725988
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152138Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74312
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant summary: AAAS c.1639dupT (p.X547LeufsX12+) causes a frameshift which results in an extension of the protein. Although this variant does not disrupt any amino acids in the encoded protein, it replaces the termination codon with 12 additional amino acids. The variant allele was found at a frequency of 6.6e-06 in 150910 control chromosomes (gnomAD v3.1.2). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1639dupT in individuals affected with Glucocorticoid Deficiency With Achalasia and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at