ENST00000490173.1:n.163G>T

Variant names:

• chr6-33320298-C-A
• rs2239839
• ENST00000490173.1:n.163G>T

Variant summary

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

The ENST00000490173.1(DAXX):​n.163G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 1,424,010 control chromosomes in the GnomAD database, including 62,287 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 (5335 hom., cov: 32)
  • Exomes 𝑓: 0.29 (56952 hom.)
• Consequence: DAXX ENST00000490173.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.644
• Publications: 30 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000490173.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAXX	NM_001141969.2	MANE Select	c.1252-74G>T		intron	N/A	NP_001135441.1
	DAXX	NM_001141970.2		c.1288-74G>T		intron	N/A	NP_001135442.1
	DAXX	NM_001350.5		c.1252-74G>T		intron	N/A	NP_001341.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAXX	ENST00000490173.1	TSL:1	n.163G>T		non_coding_transcript_exon	Exon 1 of 2
	DAXX	ENST00000374542.10	TSL:1 MANE Select	c.1252-74G>T		intron	N/A	ENSP00000363668.5
	DAXX	ENST00000266000.10	TSL:1	c.1252-74G>T		intron	N/A	ENSP00000266000.6

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35845 AN: 151964 Hom.: 5342 Cov.: 32

Gnomad AFR AF: 0.0547

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.202

GnomAD2 exomes AF: 0.298 AC: 74108 AN: 248772 AF XY: 0.302

Gnomad AFR exome AF: 0.0515

Gnomad AMR exome AF: 0.365

Gnomad ASJ exome AF: 0.222

Gnomad EAS exome AF: 0.252

Gnomad FIN exome AF: 0.371

Gnomad NFE exome AF: 0.311

Gnomad OTH exome AF: 0.287

GnomAD4 exome AF: 0.292 AC: 370916 AN: 1271928 Hom.: 56952 Cov.: 19 AF XY: 0.294 AC XY: 188881 AN XY: 642196

African (AFR) AF: 0.0448 AC: 1344 AN: 29978

American (AMR) AF: 0.357 AC: 15821 AN: 44378

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 5395 AN: 24870

East Asian (EAS) AF: 0.259 AC: 10035 AN: 38726

South Asian (SAS) AF: 0.313 AC: 25840 AN: 82438

European-Finnish (FIN) AF: 0.368 AC: 19517 AN: 53098

Middle Eastern (MID) AF: 0.169 AC: 911 AN: 5406

European-Non Finnish (NFE) AF: 0.296 AC: 277442 AN: 938762

Other (OTH) AF: 0.269 AC: 14611 AN: 54272

GnomAD4 genome AF: 0.236 AC: 35842 AN: 152082 Hom.: 5335 Cov.: 32 AF XY: 0.241 AC XY: 17938 AN XY: 74320

African (AFR) AF: 0.0545 AC: 2263 AN: 41502

American (AMR) AF: 0.303 AC: 4630 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 787 AN: 3468

East Asian (EAS) AF: 0.257 AC: 1330 AN: 5166

South Asian (SAS) AF: 0.315 AC: 1520 AN: 4826

European-Finnish (FIN) AF: 0.368 AC: 3877 AN: 10546

Middle Eastern (MID) AF: 0.134 AC: 39 AN: 292

European-Non Finnish (NFE) AF: 0.306 AC: 20816 AN: 67976

Other (OTH) AF: 0.200 AC: 422 AN: 2112

Alfa AF: 0.287 Hom.: 17934

Bravo AF: 0.219

Asia WGS AF: 0.233 AC: 811 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.1
DANN	Benign	0.61
PhyloP100		-0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2239839; hg19: chr6-33288075; COSMIC: COSV56467676; COSMIC: COSV56467676;