rs3130018

Variant names:

• chr6-33322625-G-A
• rs3130018
• NM_001141969.2:c.-53+237C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-33322625-G-A
• chr6-33322625-G-C
• chr6-33322625-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 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]

ENSG00000285064 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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.-53+237C>T		intron	N/A	NP_001135441.1
	DAXX	NM_001141970.2		c.53+237C>T		intron	N/A	NP_001135442.1
	DAXX	NM_001350.5		c.-50+237C>T		intron	N/A	NP_001341.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAXX	ENST00000374542.10	TSL:1 MANE Select	c.-53+237C>T		intron	N/A	ENSP00000363668.5
	DAXX	ENST00000266000.10	TSL:1	c.-50+237C>T		intron	N/A	ENSP00000266000.6
	ENSG00000285064	ENST00000453407.7	TSL:5	n.*100-648C>T		intron	N/A	ENSP00000408499.2

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

African (AFR) AF: 0.192 AC: 640 AN: 3328

American (AMR) AF: 0.458 AC: 2285 AN: 4986

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 2069 AN: 4262

East Asian (EAS) AF: 0.334 AC: 2679 AN: 8026

South Asian (SAS) AF: 0.616 AC: 19460 AN: 31578

European-Finnish (FIN) AF: 0.521 AC: 3695 AN: 7088

Middle Eastern (MID) AF: 0.442 AC: 265 AN: 600

European-Non Finnish (NFE) AF: 0.501 AC: 43305 AN: 86476

Other (OTH) AF: 0.490 AC: 4101 AN: 8362

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

African (AFR) AF: 0.200 AC: 8155 AN: 40770

American (AMR) AF: 0.473 AC: 7169 AN: 15156

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1703 AN: 3460

East Asian (EAS) AF: 0.379 AC: 1899 AN: 5016

South Asian (SAS) AF: 0.608 AC: 2874 AN: 4730

European-Finnish (FIN) AF: 0.525 AC: 5428 AN: 10342

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.500 AC: 33800 AN: 67640

Other (OTH) AF: 0.413 AC: 866 AN: 2096

Alfa AF: 0.447 Hom.: 21355

Bravo AF: 0.394

Asia WGS AF: 0.468 AC: 1627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.6
DANN	Benign	0.85
PhyloP100		-1.3
PromoterAI		0.030	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3130018; hg19: chr6-33290402;