7-98881202-A-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001375524.1(TRRAP):ā€‹c.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

Scores

3
5
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.39
Variant links:
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]

Genome browser will be placed here

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
TRRAPNM_001375524.1 linkc.52A>C p.Met18Leu missense_variant 2/73 ENST00000456197.2 NP_001362453.1
TRRAPNM_001244580.2 linkc.52A>C p.Met18Leu missense_variant 2/72 NP_001231509.1 Q9Y4A5-1
TRRAPNM_003496.4 linkc.52A>C p.Met18Leu missense_variant 2/71 NP_003487.1 Q9Y4A5-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TRRAPENST00000456197.2 linkc.52A>C p.Met18Leu missense_variant 2/731 NM_001375524.1 ENSP00000394645.2 H0Y4W2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152210
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000480
AC:
7
AN:
1458518
Hom.:
0
Cov.:
30
AF XY:
0.00000413
AC XY:
3
AN XY:
725532
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152210
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

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 submitterclinical testingGeneDxMay 29, 2021Not 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.39
BayesDel_addAF
Uncertain
0.063
T
BayesDel_noAF
Benign
-0.15
CADD
Uncertain
23
DANN
Benign
0.89
DEOGEN2
Benign
0.095
T;T;.;.;.
Eigen
Benign
0.024
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.93
D;D;D;D;.
M_CAP
Benign
0.0014
T
MetaRNN
Benign
0.35
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.0
.;M;M;.;.
PrimateAI
Pathogenic
0.91
D
PROVEAN
Benign
-1.9
N;N;N;.;N
REVEL
Benign
0.13
Sift
Benign
0.049
D;T;T;.;T
Sift4G
Pathogenic
0.0
D;D;D;D;D
Polyphen
0.0050, 0.0090
.;B;B;.;.
Vest4
0.45, 0.45, 0.54, 0.45
MutPred
0.31
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
0.50
MPC
0.85
ClinPred
0.66
D
GERP RS
6.1
Varity_R
0.45
gMVP
0.74

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1411933620; hg19: chr7-98478825; API