rs786201101
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_000051.4(ATM):āc.2532A>Gā(p.Gly844=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,614,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Synonymous variant affecting the same amino acid position (i.e. G844G) has been classified as Likely benign.
Frequency
Consequence
NM_000051.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATM | NM_000051.4 | c.2532A>G | p.Gly844= | synonymous_variant | 17/63 | ENST00000675843.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATM | ENST00000675843.1 | c.2532A>G | p.Gly844= | synonymous_variant | 17/63 | NM_000051.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152200Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251400Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135864
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461810Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727216
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74354
ClinVar
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 09, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Aug 22, 2018 | - - |
Likely benign, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The ATM p.Gly844= variant was not identified in the literature nor was it identified in the LOVD 3.0, database. The variant was identified in dbSNP (ID: rs755261743) as "With Likely benign allele", ClinVar (classified as likely benign by Ambry Genetics, GeneDx and Athena Diagnostics). The variant was identified in control databases in 4 of 277166 chromosomes at a frequency of 0.00001 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the European population in 4 of 126682 chromosomes (freq: 0.00003), while the variant was not observed in the African, Other, Latino, Ashkenazi Jewish, East Asian, Finnish, and South Asian populations. The p.Gly844= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, 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 although we would lean towards a more benign role for this variant. This variant is classified as likely benign. - |
Ataxia-telangiectasia syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | - - |
Familial cancer of breast Benign:1
Benign, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | May 09, 2024 | This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 18, 2018 | 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