Genetic Variant DAXX:c.-53+237C>G (chr6-33322625-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001141969.2(DAXX):c.-53+237C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DAXX
NM_001141969.2 intron

Scores

Splicing: ADA: 0.00003789

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.25

Publications

15 publications found

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:

ENSG00000285064 (HGNC:):

ENSG00000285064 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAXX	NM_001141969.2 link	c.-53+237C>G		intron_variant	Intron 1 of 7	ENST00000374542.10	NP_001135441.1	Q9UER7-1A0A024RCS3Q53F85

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAXX	ENST00000374542.10 link	c.-53+237C>G		intron_variant	Intron 1 of 7	1	NM_001141969.2	ENSP00000363668.5		Q9UER7-1
ENSG00000285064	ENST00000453407.7 link	n.*100-648C>G		intron_variant	Intron 2 of 3	5		ENSP00000408499.2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150432

Hom.:

Cov.:

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000644

AC:

AN:

155160

Hom.:

Cov.:

AF XY:

0.0000118

AC XY:

AN XY:

84494

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

3328

American (AMR)

AF:

0.00

AC:

AN:

5006

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4280

East Asian (EAS)

AF:

0.00

AC:

AN:

8052

South Asian (SAS)

AF:

0.00

AC:

AN:

31656

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7112

Middle Eastern (MID)

AF:

0.00

AC:

AN:

600

European-Non Finnish (NFE)

AF:

0.0000115

AC:

AN:

86740

Other (OTH)

AF:

0.00

AC:

AN:

8386

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

150432

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73316

African (AFR)

AF:

0.00

AC:

AN:

40682

American (AMR)

AF:

0.00

AC:

AN:

15152

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5034

South Asian (SAS)

AF:

0.00

AC:

AN:

4742

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10360

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67704

Other (OTH)

AF:

0.00

AC:

AN:

2076

Alfa

AF:

0.00

Hom.:

21355

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.9

(source)

DANN

Benign

0.41

PhyloP100

-1.3

PromoterAI

0.067

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000038

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over