ENST00000453407.7:n.*99+923T>C

Variant names:

• chr6-33323048-A-G
• rs2073525
• ENST00000453407.7:n.*99+923T>C

Variant summary

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

The ENST00000453407.7(ENSG00000285064):​n.*99+923T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 508,108 control chromosomes in the GnomAD database, including 83,303 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 0.59 (27359 hom., cov: 33)
  • Exomes 𝑓: 0.55 (55944 hom.)
• Consequence: ENSG00000285064 ENST00000453407.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 18 publications found

Genes affected

ENSG00000285064 (HGNC:):

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000453407.7. 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
	DAXX	NM_001141969.2	MANE Select	c.-239T>C		upstream_gene	N/A	NP_001135441.1
	DAXX	NM_001141970.2		c.-134T>C		upstream_gene	N/A	NP_001135442.1
	DAXX	NM_001350.5		c.-236T>C		upstream_gene	N/A	NP_001341.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000285064	ENST00000453407.7	TSL:5	n.*99+923T>C		intron	N/A	ENSP00000408499.2
	DAXX	ENST00000859774.1		c.-137T>C		5_prime_UTR	Exon 1 of 8	ENSP00000529833.1
	DAXX	ENST00000374542.10	TSL:1 MANE Select	c.-239T>C		upstream_gene	N/A	ENSP00000363668.5

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89929 AN: 152020 Hom.: 27313 Cov.: 33

Gnomad AFR AF: 0.737

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.583

GnomAD4 exome AF: 0.555 AC: 197544 AN: 355970 Hom.: 55944 Cov.: 4 AF XY: 0.563 AC XY: 107169 AN XY: 190268

African (AFR) AF: 0.737 AC: 8097 AN: 10982

American (AMR) AF: 0.551 AC: 13806 AN: 25064

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 6895 AN: 12002

East Asian (EAS) AF: 0.393 AC: 7435 AN: 18942

South Asian (SAS) AF: 0.658 AC: 35371 AN: 53790

European-Finnish (FIN) AF: 0.526 AC: 13248 AN: 25166

Middle Eastern (MID) AF: 0.591 AC: 1764 AN: 2986

European-Non Finnish (NFE) AF: 0.533 AC: 100363 AN: 188404

Other (OTH) AF: 0.567 AC: 10565 AN: 18634

GnomAD4 genome AF: 0.592 AC: 90028 AN: 152138 Hom.: 27359 Cov.: 33 AF XY: 0.592 AC XY: 44045 AN XY: 74342

African (AFR) AF: 0.737 AC: 30621 AN: 41522

American (AMR) AF: 0.576 AC: 8801 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 2004 AN: 3472

East Asian (EAS) AF: 0.420 AC: 2169 AN: 5162

South Asian (SAS) AF: 0.652 AC: 3150 AN: 4832

European-Finnish (FIN) AF: 0.526 AC: 5564 AN: 10574

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.529 AC: 35974 AN: 67986

Other (OTH) AF: 0.581 AC: 1225 AN: 2110

Alfa AF: 0.574 Hom.: 35074

Bravo AF: 0.599

Asia WGS AF: 0.533 AC: 1855 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.56
DANN	Benign	0.74
PhyloP100		-1.5
PromoterAI		-0.023	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2073525; hg19: chr6-33290825; COSMIC: COSV56467678;