rs946541820
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_000051.4(ATM):c.6348-3C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,448,334 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000051.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATM | NM_000051.4 | c.6348-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000675843.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATM | ENST00000675843.1 | c.6348-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | NM_000051.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000803 AC: 2AN: 248940Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134780
GnomAD4 exome AF: 0.00000207 AC: 3AN: 1448334Hom.: 0 Cov.: 29 AF XY: 0.00000416 AC XY: 3AN XY: 721498
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 07, 2016 | The c.6348-3C>T intronic alteration consists of a C to T substitution 3 nucleotides before coding exon 43 in the ATM gene. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Dec 27, 2022 | - - |
Ataxia-telangiectasia syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 14, 2023 | This sequence change falls in intron 43 of the ATM gene. It does not directly change the encoded amino acid sequence of the ATM protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has been observed in individual(s) with hereditary breast and ovarian cancer (PMID: 12810666). This variant is also known as IVS45-3C>T. ClinVar contains an entry for this variant (Variation ID: 453623). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at