Variant 7-98881188-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_001375524.1(TRRAP):c.38A>C(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 (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TRRAP
NM_001375524.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.14

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]

TRRAP links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), TRRAP. . Gene score misZ 8.173 (greater than the threshold 3.09). Trascript score misZ 10.503 (greater than threshold 3.09). GenCC has associacion of gene with autosomal dominant nonsyndromic hearing loss, developmental delay with or without dysmorphic facies and autism, hearing loss, autosomal dominant 75, complex neurodevelopmental disorder with or without congenital anomalies.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TRRAP	NM_001375524.1 linkuse as main transcript	c.38A>C	p.Asp13Ala	missense_variant	2/73	ENST00000456197.2
TRRAP	NM_001244580.2 linkuse as main transcript	c.38A>C	p.Asp13Ala	missense_variant	2/72
TRRAP	NM_003496.4 linkuse as main transcript	c.38A>C	p.Asp13Ala	missense_variant	2/71

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRRAP	ENST00000456197.2 linkuse as main transcript	c.38A>C	p.Asp13Ala	missense_variant	2/73	1	NM_001375524.1	P2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458910

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725714

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.88

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

T;T;.;.;.

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

D;D;D;D;.

M_CAP

Benign

0.0071

MetaRNN

Uncertain

0.71

D;D;D;D;D

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.8

.;L;L;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-3.4

D;N;N;.;N

REVEL

Uncertain

0.48

Sift

Benign

0.16

T;D;D;.;D

Sift4G

Pathogenic

0.0

D;T;T;T;T

Polyphen

0.99, 1.0

.;D;D;.;.

Vest4

0.69, 0.67, 0.89, 0.71

MutPred

0.58

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

0.50

MPC

1.7

ClinPred

0.95

GERP RS

5.9

Varity_R

0.63

gMVP

0.95

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over