chr11-108316008-T-C
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_000051.4(ATM):c.6096-3T>C 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 0.00000479 in 1,461,664 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 -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATM | NM_000051.4 | c.6096-3T>C | 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.6096-3T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | NM_000051.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251346Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135846
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461664Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727150
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Ataxia-telangiectasia syndrome Uncertain:1Benign:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | May 26, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 19, 2023 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden | Nov 03, 2021 | - - |
Familial ovarian cancer Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The ATM c.6096-3T>C variant was not identified in the literature nor was it identified in the COGR, Cosmic, or LOVD 3.0 databases. The variant was identified in dbSNP (ID: rs748380897) as "With Uncertain significance allele" and ClinVar (classified as uncertain significance by Invitae and Ambry Genetics). The variant was identified in control databases in 2 of 246130 chromosomes at a frequency of 0.000008 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European in 1 of 111648 chromosomes (freq: 0.000009) and East Asian in 1 of 17212 chromosomes (freq: 0.00006); it was not observed in the African, Other, Latino, Ashkenazi Jewish, Finnish, or South Asian populations. The c.6096-3T>C variant is located in the 3' splice region and does not affect the invariant -1 and -2 positions, although positions -3 and -5 to -12 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. However, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 23, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at