rs3130018

chr6-33322625-G-Achr6-33322625-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001141969.2(DAXX):c.-53+237C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 305,114 control chromosomes in the GnomAD database, including 35,130 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 0.41 (14336 hom., cov: 28)
  • Exomes 𝑓: 0.51 (20794 hom.)
• Consequence: DAXX NM_001141969.2 intron
• Scores: Splicing: ADA: 0.00004088
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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]

LOC124901303 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAXX	NM_001141969.2	c.-53+237C>T		intron_variant		ENST00000374542.10
LOC124901303	XR_007059547.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAXX	ENST00000374542.10	c.-53+237C>T		intron_variant		1	NM_001141969.2	P2

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62293 AN: 150290 Hom.: 14331 Cov.: 28

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.413

GnomAD4 exome AF: 0.507 AC: 78499 AN: 154706 Hom.: 20794 Cov.: 0 AF XY: 0.522 AC XY: 44001 AN XY: 84254

Gnomad4 AFR exome AF: 0.192

Gnomad4 AMR exome AF: 0.458

Gnomad4 ASJ exome AF: 0.485

Gnomad4 EAS exome AF: 0.334

Gnomad4 SAS exome AF: 0.616

Gnomad4 FIN exome AF: 0.521

Gnomad4 NFE exome AF: 0.501

Gnomad4 OTH exome AF: 0.490

GnomAD4 genome AF: 0.414 AC: 62335 AN: 150408 Hom.: 14336 Cov.: 28 AF XY: 0.421 AC XY: 30869 AN XY: 73348

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.492

Gnomad4 EAS AF: 0.379

Gnomad4 SAS AF: 0.608

Gnomad4 FIN AF: 0.525

Gnomad4 NFE AF: 0.500

Gnomad4 OTH AF: 0.413

Alfa AF: 0.473 Hom.: 10335

Bravo AF: 0.394

Asia WGS AF: 0.468 AC: 1627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	3.6
Dann	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000041
dbscSNV1_RF	Benign	0.0040
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

Other links and lift over

dbSNP: rs3130018; hg19: chr6-33290402;