chr7-98890342-C-T
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP6_ModerateBS1BS2
The NM_001375524.1(TRRAP):c.158C>T(p.Thr53Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000964 in 1,556,790 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: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000093 ( 0 hom. )
Consequence
TRRAP
NM_001375524.1 missense
NM_001375524.1 missense
Scores
3
3
12
Clinical Significance
Conservation
PhyloP100: 7.83
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 Benign. Variant got -9 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, TRRAP
BP6
?
Variant 7-98890342-C-T is Benign according to our data. Variant chr7-98890342-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2256201.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000131 (2/152224) while in subpopulation SAS AF= 0.000415 (2/4820). AF 95% confidence interval is 0.000073. There are 0 homozygotes in gnomad4. There are 2 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAdExome at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRRAP | NM_001375524.1 | c.158C>T | p.Thr53Met | missense_variant | 4/73 | ENST00000456197.2 | |
TRRAP | NM_001244580.2 | c.158C>T | p.Thr53Met | missense_variant | 4/72 | ||
TRRAP | NM_003496.4 | c.158C>T | p.Thr53Met | missense_variant | 4/71 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRRAP | ENST00000456197.2 | c.158C>T | p.Thr53Met | missense_variant | 4/73 | 1 | NM_001375524.1 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152106Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000239 AC: 5AN: 209346Hom.: 0 AF XY: 0.0000439 AC XY: 5AN XY: 113936
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GnomAD4 exome AF: 0.00000926 AC: 13AN: 1404566Hom.: 0 Cov.: 29 AF XY: 0.0000143 AC XY: 10AN XY: 697412
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74426
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 27, 2021 | 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
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
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N;.;N
REVEL
Uncertain
Sift
Benign
T;T;T;.;T
Sift4G
Pathogenic
D;T;T;T;T
Polyphen
0.96, 0.97
.;D;D;.;.
Vest4
0.59, 0.60, 0.58, 0.61
MutPred
Loss of glycosylation at T53 (P = 0.0223);Loss of glycosylation at T53 (P = 0.0223);Loss of glycosylation at T53 (P = 0.0223);Loss of glycosylation at T53 (P = 0.0223);Loss of glycosylation at T53 (P = 0.0223);
MVP
MPC
1.8
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 14
Find out detailed SpliceAI scores and Pangolin per-transcript scores at