11-108243969-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5
The NM_000051.4(ATM):c.513C>T(p.Tyr171Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000051.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATM | NM_000051.4 | c.513C>T | p.Tyr171Tyr | synonymous_variant | Exon 6 of 63 | ENST00000675843.1 | NP_000042.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00 AC: 0AN: 148666Hom.: 0 Cov.: 32 FAILED QC
GnomAD4 exome Cov.: 33
GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 148666Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 72152
ClinVar
Submissions by phenotype
Ataxia-telangiectasia syndrome Pathogenic:2Uncertain:1
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This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with ataxia-telangiectasia (PMID: 14695534). ClinVar contains an entry for this variant (Variation ID: 802727). Studies have shown that this variant results in activation of a cryptic splice site and introduces a premature termination codon (PMID: 14695534). The resulting mRNA is expected to undergo nonsense-mediated decay. This sequence change affects codon 171 of the ATM mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the ATM protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. 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. -
ATM-related disorder Pathogenic:1
The ATM c.513C>T variant is not predicted to result in an amino acid change (p.=). This variant has been reported as homozygous in an individual with ataxia telangiectasia (Table 1, Eng et al. 2004. PubMed ID: 14695534). Although this variant results in a silent protein change, it causes a splicing defect by activating a cryptic splice site that results in a premature termination codon (Eng et al. 2004. PubMed ID: 14695534). This variant has not been reported in a large population database, indicating this variant is rare. This variant has conflicting interpretations regarding its pathogenicity in ClinVar, ranging from uncertain to likely pathogenic (https://www.ncbi.nlm.nih.gov/clinvar/variation/802727/). This variant is interpreted as likely pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at