chr11-108317510-C-T
Variant names:
Variant summary
Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_000051.4(ATM):c.6336C>T(p.Cys2112Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,640 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 (★★).
Frequency
Genomes: not found (cov: 28)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
ATM
NM_000051.4 synonymous
NM_000051.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.241
Publications
0 publications found
Genes affected
ATM (HGNC:795): (ATM serine/threonine kinase) The protein encoded by this gene belongs to the PI3/PI4-kinase family. This protein is an important cell cycle checkpoint kinase that phosphorylates; thus, it functions as a regulator of a wide variety of downstream proteins, including tumor suppressor proteins p53 and BRCA1, checkpoint kinase CHK2, checkpoint proteins RAD17 and RAD9, and DNA repair protein NBS1. This protein and the closely related kinase ATR are thought to be master controllers of cell cycle checkpoint signaling pathways that are required for cell response to DNA damage and for genome stability. Mutations in this gene are associated with ataxia telangiectasia, an autosomal recessive disorder. [provided by RefSeq, Aug 2010]
C11orf65 (HGNC:28519): (chromosome 11 open reading frame 65) Predicted to be involved in negative regulation of mitochondrial fission and negative regulation of protein targeting to mitochondrion. Predicted to be located in cytosol and mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 11-108317510-C-T is Benign according to our data. Variant chr11-108317510-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 453622.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.241 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000051.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ATM | NM_000051.4 | MANE Select | c.6336C>T | p.Cys2112Cys | synonymous | Exon 43 of 63 | NP_000042.3 | ||
| ATM | NM_001351834.2 | c.6336C>T | p.Cys2112Cys | synonymous | Exon 44 of 64 | NP_001338763.1 | |||
| C11orf65 | NM_001330368.2 | c.641-8439G>A | intron | N/A | NP_001317297.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ATM | ENST00000675843.1 | MANE Select | c.6336C>T | p.Cys2112Cys | synonymous | Exon 43 of 63 | ENSP00000501606.1 | ||
| ATM | ENST00000452508.7 | TSL:1 | c.6336C>T | p.Cys2112Cys | synonymous | Exon 44 of 64 | ENSP00000388058.2 | ||
| ATM | ENST00000527805.6 | TSL:1 | n.*1400C>T | non_coding_transcript_exon | Exon 41 of 61 | ENSP00000435747.2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
28
GnomAD2 exomes AF: 0.00000800 AC: 2AN: 250006 AF XY: 0.0000148 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
250006
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1457640Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 725206 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
1457640
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
725206
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33298
American (AMR)
AF:
AC:
0
AN:
44628
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25942
East Asian (EAS)
AF:
AC:
0
AN:
39456
South Asian (SAS)
AF:
AC:
1
AN:
86102
European-Finnish (FIN)
AF:
AC:
0
AN:
52970
Middle Eastern (MID)
AF:
AC:
0
AN:
5740
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1109382
Other (OTH)
AF:
AC:
0
AN:
60122
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
28
ClinVar
ClinVar submissions as Germline
Significance:Benign/Likely benign
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
-
-
1
Ataxia-telangiectasia syndrome (1)
-
-
1
Familial cancer of breast (1)
-
-
1
Hereditary cancer-predisposing syndrome (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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