rs1555066242
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PM4_Supporting
The NM_000051.4(ATM):c.501_503del(p.Leu167del) variant causes a inframe deletion, splice region change. The variant allele was found at a frequency of 0.000000714 in 1,400,704 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. L167L) has been classified as Likely benign.
Frequency
Consequence
NM_000051.4 inframe_deletion, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATM | NM_000051.4 | c.501_503del | p.Leu167del | inframe_deletion, splice_region_variant | 6/63 | ENST00000675843.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATM | ENST00000675843.1 | c.501_503del | p.Leu167del | inframe_deletion, splice_region_variant | 6/63 | NM_000051.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome AF: 7.14e-7 AC: 1AN: 1400704Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 692680
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Ataxia-telangiectasia syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2023 | This variant, c.501_503del, results in the deletion of 1 amino acid(s) of the ATM protein (p.Leu167del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. RNA analysis performed to evaluate the impact of this variant on mRNA splicing indicates it does not significantly alter splicing (Invitae). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 453552). This variant has not been reported in the literature in individuals affected with ATM-related conditions. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at