NM_001375524.1:c.5731-754C>T

Variant names:

• chr7-98954344-C-T
• rs3801246
• NM_001375524.1:c.5731-754C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001375524.1(TRRAP):​c.5731-754C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 152,232 control chromosomes in the GnomAD database, including 41,679 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.70 (41679 hom., cov: 34)
• Consequence: TRRAP NM_001375524.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.251
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder with or without congenital anomalies

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• developmental delay with or without dysmorphic facies and autism

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hearing loss, autosomal dominant 75

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375524.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRRAP	NM_001375524.1	MANE Select	c.5731-754C>T		intron	N/A	NP_001362453.1
	TRRAP	NM_001244580.2		c.5710-754C>T		intron	N/A	NP_001231509.1
	TRRAP	NM_003496.4		c.5656-754C>T		intron	N/A	NP_003487.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRRAP	ENST00000456197.2	TSL:1 MANE Select	c.5731-754C>T		intron	N/A	ENSP00000394645.2
	TRRAP	ENST00000359863.8	TSL:1	c.5710-754C>T		intron	N/A	ENSP00000352925.4
	TRRAP	ENST00000355540.7	TSL:1	c.5656-754C>T		intron	N/A	ENSP00000347733.3

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106364 AN: 152114 Hom.: 41668 Cov.: 34

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.883

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.871

Gnomad FIN AF: 0.865

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.871

Gnomad OTH AF: 0.742

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.699 AC: 106388 AN: 152232 Hom.: 41679 Cov.: 34 AF XY: 0.703 AC XY: 52329 AN XY: 74440

African (AFR) AF: 0.311 AC: 12908 AN: 41502

American (AMR) AF: 0.768 AC: 11749 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 2762 AN: 3468

East Asian (EAS) AF: 0.723 AC: 3751 AN: 5186

South Asian (SAS) AF: 0.872 AC: 4215 AN: 4832

European-Finnish (FIN) AF: 0.865 AC: 9184 AN: 10616

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.871 AC: 59220 AN: 68014

Other (OTH) AF: 0.746 AC: 1576 AN: 2114

Alfa AF: 0.758 Hom.: 8177

Bravo AF: 0.672

Asia WGS AF: 0.788 AC: 2743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.6
DANN	Benign	0.46
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3801246; hg19: chr7-98551967;