10-121899963-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001001976.3(ATE1):c.845C>T(p.Ser282Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,461,574 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000010 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
ATE1
NM_001001976.3 missense
NM_001001976.3 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 5.69
Genes affected
ATE1 (HGNC:782): (arginyltransferase 1) This gene encodes an arginyltransferase, an enzyme that is involved in posttranslational conjugation of arginine to N-terminal aspartate or glutamate residues. Conjugation of arginine to the N-terminal aspartate or glutamate targets proteins for ubiquitin-dependent degradation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13407579).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATE1 | NM_001001976.3 | c.845C>T | p.Ser282Leu | missense_variant | 7/12 | ENST00000224652.12 | NP_001001976.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ATE1 | ENST00000224652.12 | c.845C>T | p.Ser282Leu | missense_variant | 7/12 | 1 | NM_001001976.3 | ENSP00000224652 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 5AN: 152042Hom.: 0 Cov.: 33 FAILED QC
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251416Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135884
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GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461574Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8AN XY: 727120
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000329 AC: 5AN: 152160Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74370
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Data not reliable, filtered out with message: AS_VQSR
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 15, 2021 | The c.845C>T (p.S282L) alteration is located in exon 7 (coding exon 7) of the ATE1 gene. This alteration results from a C to T substitution at nucleotide position 845, causing the serine (S) at amino acid position 282 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D;D;D;N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
D;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Benign
T;T
Polyphen
P;.
Vest4
MutPred
Gain of sheet (P = 0.0101);.;
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at