7-98881202-A-C
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_001375524.1(TRRAP):āc.52A>Cā(p.Met18Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000497 in 1,610,728 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 (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 31)
Exomes š: 0.0000048 ( 0 hom. )
Consequence
TRRAP
NM_001375524.1 missense
NM_001375524.1 missense
Scores
3
5
11
Clinical Significance
Conservation
PhyloP100: 7.39
Genes affected
TRRAP (HGNC:12347): (transformation/transcription domain associated protein) This gene encodes a large multidomain protein of the phosphoinositide 3-kinase-related kinases (PIKK) family. The encoded protein is a common component of many histone acetyltransferase (HAT) complexes and plays a role in transcription and DNA repair by recruiting HAT complexes to chromatin. Deregulation of this gene may play a role in several types of cancer including glioblastoma multiforme. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.35103667).
BS2
High AC in GnomAdExome4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TRRAP | NM_001375524.1 | c.52A>C | p.Met18Leu | missense_variant | 2/73 | ENST00000456197.2 | NP_001362453.1 | |
TRRAP | NM_001244580.2 | c.52A>C | p.Met18Leu | missense_variant | 2/72 | NP_001231509.1 | ||
TRRAP | NM_003496.4 | c.52A>C | p.Met18Leu | missense_variant | 2/71 | NP_003487.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152210Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 0.00000480 AC: 7AN: 1458518Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 725532
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152210Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74374
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 29, 2021 | Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533) - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
DEOGEN2
Benign
T;T;.;.;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;.
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M;M;.;.
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N;.;N
REVEL
Benign
Sift
Benign
D;T;T;.;T
Sift4G
Pathogenic
D;D;D;D;D
Polyphen
0.0050, 0.0090
.;B;B;.;.
Vest4
0.45, 0.45, 0.54, 0.45
MutPred
Loss of methylation at K20 (P = 0.0815);Loss of methylation at K20 (P = 0.0815);Loss of methylation at K20 (P = 0.0815);Loss of methylation at K20 (P = 0.0815);Loss of methylation at K20 (P = 0.0815);
MVP
MPC
0.85
ClinPred
D
GERP RS
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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