rs760058702
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The NM_000051.4(ATM):c.6976-6dup 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 0.00000186 in 1,611,246 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 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 Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATM | NM_000051.4 | c.6976-6dup | 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.6976-6dup | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | NM_000051.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152198Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1459048Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 726020
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152198Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74358
ClinVar
Submissions by phenotype
Hereditary breast ovarian cancer syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Pittsburgh Clinical Genomics Laboratory, University of Pittsburgh Medical Center | Apr 16, 2018 | This sequence variant in ATM results from a duplication of a single nucleotide (dupA) at the -6 position in the splice acceptor region of intron 47. c.6976-6dupA occurs at the border of the polypyrimidine region of the splice site and it is unclear whether it affects splicing. Bioinformatic splicing tools predict no effect on splicing but there is no functional evidence to support this assertion. This rare variant has been reported in gnomAD at a frequency of 0.003% (1/30,976 alleles). It has not been reported to be associated with ataxia telangiectasia or hereditary cancer. c.6976-6dupA has been reported by another laboratory in ClinVar (RSV0004723561) as Likely Benign but the evidence for this assertion is not provided. The clinical significance of this variant is uncertain at this time. - |
Ataxia-telangiectasia syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 27, 2023 | - - |
Familial cancer of breast Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Jun 12, 2024 | This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at