6-33320494-A-G

Variant names:

• chr6-33320494-A-G
• rs1059231
• NM_001141969.2:c.1137T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001141969.2(DAXX):​c.1137T>C​(p.Tyr379Tyr) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.226
• Publications: 37 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001141969.2. 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.1137T>C	p.Tyr379Tyr	synonymous	Exon 4 of 8	NP_001135441.1
	DAXX	NM_001141970.2		c.1173T>C	p.Tyr391Tyr	synonymous	Exon 4 of 8	NP_001135442.1
	DAXX	NM_001350.5		c.1137T>C	p.Tyr379Tyr	synonymous	Exon 4 of 8	NP_001341.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAXX	ENST00000374542.10	TSL:1 MANE Select	c.1137T>C	p.Tyr379Tyr	synonymous	Exon 4 of 8	ENSP00000363668.5
	DAXX	ENST00000266000.10	TSL:1	c.1137T>C	p.Tyr379Tyr	synonymous	Exon 4 of 8	ENSP00000266000.6
	DAXX	ENST00000706094.1		c.1173T>C	p.Tyr391Tyr	synonymous	Exon 4 of 8	ENSP00000516212.1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35890 AN: 151966 Hom.: 5359 Cov.: 32

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

GnomAD2 exomes AF: 0.298 AC: 74877 AN: 251304 AF XY: 0.303

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 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.: 33 AF XY: 0.296 AC XY: 215456 AN XY: 726704

African (AFR) AF: 0.0444 AC: 1485 AN: 33472

American (AMR) AF: 0.357 AC: 15944 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 5686 AN: 26126

East Asian (EAS) AF: 0.260 AC: 10312 AN: 39694

South Asian (SAS) AF: 0.315 AC: 27140 AN: 86242

European-Finnish (FIN) AF: 0.367 AC: 19586 AN: 53320

Middle Eastern (MID) AF: 0.171 AC: 988 AN: 5766

European-Non Finnish (NFE) AF: 0.300 AC: 332778 AN: 1110848

Other (OTH) AF: 0.272 AC: 16409 AN: 60348

GnomAD4 genome AF: 0.236 AC: 35887 AN: 152084 Hom.: 5352 Cov.: 32 AF XY: 0.242 AC XY: 17974 AN XY: 74334

African (AFR) AF: 0.0547 AC: 2272 AN: 41514

American (AMR) AF: 0.303 AC: 4623 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 787 AN: 3472

East Asian (EAS) AF: 0.257 AC: 1331 AN: 5178

South Asian (SAS) AF: 0.315 AC: 1520 AN: 4824

European-Finnish (FIN) AF: 0.370 AC: 3905 AN: 10552

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20824 AN: 67966

Other (OTH) AF: 0.201 AC: 424 AN: 2112

Alfa AF: 0.257 Hom.: 8700

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	-0.77
CADD	Benign	3.3
DANN	Benign	0.77
PhyloP100		-0.23
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1059231; hg19: chr6-33288271; COSMIC: COSV56466529; COSMIC: COSV56466529;