chr7-98881188-A-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001375524.1(TRRAP):āc.38A>Cā(p.Asp13Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,910 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 31)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
TRRAP
NM_001375524.1 missense
NM_001375524.1 missense
Scores
7
6
6
Clinical Significance
Conservation
PhyloP100: 9.14
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TRRAP | NM_001375524.1 | c.38A>C | p.Asp13Ala | missense_variant | 2/73 | ENST00000456197.2 | NP_001362453.1 | |
TRRAP | NM_001244580.2 | c.38A>C | p.Asp13Ala | missense_variant | 2/72 | NP_001231509.1 | ||
TRRAP | NM_003496.4 | c.38A>C | p.Asp13Ala | missense_variant | 2/71 | NP_003487.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1458910Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 725714
GnomAD4 exome
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2
AN:
1458910
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Cov.:
30
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0
AN XY:
725714
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
TRRAP-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 25, 2022 | The TRRAP c.38A>C variant is predicted to result in the amino acid substitution p.Asp13Ala. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;.
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;L;.;.
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;N;N;.;N
REVEL
Uncertain
Sift
Benign
T;D;D;.;D
Sift4G
Pathogenic
D;T;T;T;T
Polyphen
0.99, 1.0
.;D;D;.;.
Vest4
0.69, 0.67, 0.89, 0.71
MutPred
Gain of MoRF binding (P = 0.0461);Gain of MoRF binding (P = 0.0461);Gain of MoRF binding (P = 0.0461);Gain of MoRF binding (P = 0.0461);Gain of MoRF binding (P = 0.0461);
MVP
MPC
1.7
ClinPred
D
GERP RS
Varity_R
gMVP
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
No publications associated with this variant yet.