Variant rs1059231 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001141969.2(DAXX):c.1137T>C(p.Tyr379=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 1,612,622 control chromosomes in the GnomAD database, including 71,056 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 0.24 ( 5352 hom., cov: 32)

Exomes 𝑓: 0.29 ( 65704 hom. )

Consequence

DAXX
NM_001141969.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.226

Variant links:

Genes affected

DAXX (HGNC:2681): (death domain associated protein) This gene encodes a multifunctional protein that resides in multiple locations in the nucleus and in the cytoplasm. It interacts with a wide variety of proteins, such as apoptosis antigen Fas, centromere protein C, and transcription factor erythroblastosis virus E26 oncogene homolog 1. In the nucleus, the encoded protein functions as a potent transcription repressor that binds to sumoylated transcription factors. Its repression can be relieved by the sequestration of this protein into promyelocytic leukemia nuclear bodies or nucleoli. This protein also associates with centromeres in G2 phase. In the cytoplasm, the encoded protein may function to regulate apoptosis. The subcellular localization and function of this protein are modulated by post-translational modifications, including sumoylation, phosphorylation and polyubiquitination. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2008]

DAXX links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP7

Synonymous conserved (PhyloP=-0.226 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAXX	NM_001141969.2 linkuse as main transcript	c.1137T>C	p.Tyr379=	synonymous_variant	4/8	ENST00000374542.10	NP_001135441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAXX	ENST00000374542.10 linkuse as main transcript	c.1137T>C	p.Tyr379=	synonymous_variant	4/8	1	NM_001141969.2	ENSP00000363668	P2	Q9UER7-1

Frequencies

GnomAD3 genomes

AF:

0.236

AC:

35890

AN:

151966

Hom.:

5359

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0549

Gnomad AMI

AF:

0.175

Gnomad AMR

AF:

0.303

Gnomad ASJ

AF:

0.227

Gnomad EAS

AF:

0.257

Gnomad SAS

AF:

0.315

Gnomad FIN

AF:

0.370

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.306

Gnomad OTH

AF:

0.203

GnomAD3 exomes

AF:

0.298

AC:

74877

AN:

251304

Hom.:

12090

AF XY:

0.303

AC XY:

41091

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.0515

Gnomad AMR exome

AF:

0.365

Gnomad ASJ exome

AF:

0.221

Gnomad EAS exome

AF:

0.252

Gnomad SAS exome

AF:

0.310

Gnomad FIN exome

AF:

0.370

Gnomad NFE exome

AF:

0.311

Gnomad OTH exome

AF:

0.287

GnomAD4 exome

AF:

0.295

AC:

430328

AN:

1460538

Hom.:

65704

Cov.:

AF XY:

0.296

AC XY:

215456

AN XY:

726704

show subpopulations

Gnomad4 AFR exome

AF:

0.0444

Gnomad4 AMR exome

AF:

0.357

Gnomad4 ASJ exome

AF:

0.218

Gnomad4 EAS exome

AF:

0.260

Gnomad4 SAS exome

AF:

0.315

Gnomad4 FIN exome

AF:

0.367

Gnomad4 NFE exome

AF:

0.300

Gnomad4 OTH exome

AF:

0.272

GnomAD4 genome

AF:

0.236

AC:

35887

AN:

152084

Hom.:

5352

Cov.:

AF XY:

0.242

AC XY:

17974

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0547

Gnomad4 AMR

AF:

0.303

Gnomad4 ASJ

AF:

0.227

Gnomad4 EAS

AF:

0.257

Gnomad4 SAS

AF:

0.315

Gnomad4 FIN

AF:

0.370

Gnomad4 NFE

AF:

0.306

Gnomad4 OTH

AF:

0.201

Alfa

AF:

0.283

Hom.:

5275

Bravo

AF:

0.219

Asia WGS

AF:

0.233

AC:

811

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

3.3

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over