rs1555093241
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_000051.4(ATM):c.3747-16A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000254 in 1,573,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000051.4 splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATM | NM_000051.4 | c.3747-16A>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000675843.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATM | ENST00000675843.1 | c.3747-16A>G | splice_polypyrimidine_tract_variant, intron_variant | NM_000051.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152066Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000211 AC: 3AN: 1421862Hom.: 0 Cov.: 29 AF XY: 0.00000141 AC XY: 1AN XY: 707822
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152066Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74260
ClinVar
Submissions by phenotype
Ataxia-telangiectasia syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 18, 2023 | This sequence change falls in intron 25 of the ATM gene. It does not directly change the encoded amino acid sequence of the ATM protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 490545). Studies have shown that this variant results in skipping of part of exon 26 and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. - |
Familial cancer of breast Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | May 23, 2022 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 26, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jun 06, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at