11-108310161-CCTT-C
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PM4_Supporting
The NM_000051.4(ATM):โc.5769_5771delโ(p.Ser1924del) variant causes a inframe deletion, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,612,680 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). Synonymous variant affecting the same amino acid position (i.e. P1922P) 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.5769_5771del | p.Ser1924del | inframe_deletion, splice_region_variant | 39/63 | ENST00000675843.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATM | ENST00000675843.1 | c.5769_5771del | p.Ser1924del | inframe_deletion, splice_region_variant | 39/63 | NM_000051.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152036Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250570Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135612
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460644Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 726658
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152036Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74238
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 10, 2023 | The c.5769_5771delTTC variant (also known as p.S1924del) is located in coding exon 38 of the ATM gene. This variant results from an in-frame TTC deletion at nucleotide positions 5769 to 5771. This results in the in-frame deletion of a serine at codon 1924. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Apr 27, 2016 | - - |
Ataxia-telangiectasia syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 17, 2023 | This variant, c.5769_5771del, results in the deletion of 1 amino acid(s) of the ATM protein (p.Ser1924del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 419402). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 14, 2015 | This deletion of 3 nucleotides in ATM is denoted c.5769_5771delTTC at the cDNA level and p.Ser1924del (S1924del) at the protein level. The normal sequence, with the bases that are deleted in braces, is CTTC[TTC]AGGA. This in frame deletion of a single Serine residue occurs at a position that is not conserved across species and is not located in a known functional domain (Uniprot). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. Since in frame deletions may or may not inhibit proper protein functioning, the clinical significance of this finding remains unclear at this time and we consider ATM Ser1924del to be a variant of uncertain significance. - |
Familial cancer of breast Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Sep 13, 2023 | This variant, c.5769_5771del, results in the deletion of 1 amino acid(s) of the ATM protein (p.Ser1924del),This in frame deletions may or may not inhibit proper protein functioning as in frame deletion preserves the integrity of the reading frame. . This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 419402). This amino acid position is not well conserved ( phyloP=0.91, 2.86, 0.27, 1.18) and is not located in a known functional domain (Uniprot). In addition, the in silico prediction for this alteration is inconclusive. 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