rs768565424
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP3BP6
The NM_000051.4(ATM):c.5004A>G(p.Leu1668=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to 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. L1668L) has been classified as Likely benign.
Frequency
Consequence
NM_000051.4 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATM | NM_000051.4 | c.5004A>G | p.Leu1668= | splice_region_variant, synonymous_variant | 33/63 | ENST00000675843.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATM | ENST00000675843.1 | c.5004A>G | p.Leu1668= | splice_region_variant, synonymous_variant | 33/63 | NM_000051.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250642Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135500
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1460218Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 726524
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Ataxia-telangiectasia syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 08, 2023 | This sequence change affects codon 1668 of the ATM mRNA. It is a 'silent' change, meaning that it does not 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 (rs768565424, gnomAD 0.003%). This variant has been observed in individual(s) with breast cancer (PMID: 30287823). ClinVar contains an entry for this variant (Variation ID: 578601). RNA analysis performed to evaluate the impact of this variant on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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. - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 19, 2023 | 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