Variant 18-33578991-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_030632.3(ASXL3):c.54+306C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0553 in 174,394 control chromosomes in the GnomAD database, including 339 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.053 ( 278 hom., cov: 32)

Exomes 𝑓: 0.073 ( 61 hom. )

Consequence

ASXL3
NM_030632.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.840

Variant links:

Genes affected

ASXL3 (HGNC:29357): (ASXL transcriptional regulator 3) This gene encodes a protein containing a plant homeodomain (PHD) zinc finger domain that plays a role in the regulation of gene transcription. The encoded protein has been shown to negatively regulate lipogenesis by binding to and inhibiting the transcriptional activity of two nuclear hormone receptors, oxysterols receptor LXR-alpha (LXRalpha) and thyroid hormone receptor beta (TRbeta). The encoded protein may also inhibit histone deubiquitination. Mutations in this gene have been identified in human patients with Bainbridge-Ropers syndrome, which is characterized by feeding difficulties, developmental delay and other features. [provided by RefSeq, May 2017]

ASXL3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 18-33578991-C-T is Benign according to our data. Variant chr18-33578991-C-T is described in ClinVar as [Benign]. Clinvar id is 1225338.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.069 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASXL3	NM_030632.3 linkuse as main transcript	c.54+306C>T		intron_variant		ENST00000269197.12
ASXL3	XM_005258356.2 linkuse as main transcript	c.54+306C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASXL3	ENST00000269197.12 linkuse as main transcript	c.54+306C>T		intron_variant		5	NM_030632.3	P4	Q9C0F0-1

Frequencies

GnomAD3 genomes

AF:

0.0527

AC:

8026

AN:

152182

Hom.:

279

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0142

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.0693

Gnomad ASJ

AF:

0.0908

Gnomad EAS

AF:

0.0705

Gnomad SAS

AF:

0.0745

Gnomad FIN

AF:

0.0517

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0677

Gnomad OTH

AF:

0.0659

GnomAD4 exome

AF:

0.0731

AC:

1615

AN:

22094

Hom.:

Cov.:

AF XY:

0.0739

AC XY:

909

AN XY:

12308

show subpopulations

Gnomad4 AFR exome

AF:

0.00830

Gnomad4 AMR exome

AF:

0.0728

Gnomad4 ASJ exome

AF:

0.134

Gnomad4 EAS exome

AF:

0.119

Gnomad4 SAS exome

AF:

0.0885

Gnomad4 FIN exome

AF:

0.0537

Gnomad4 NFE exome

AF:

0.0736

Gnomad4 OTH exome

AF:

0.0649

GnomAD4 genome

AF:

0.0527

AC:

8023

AN:

152300

Hom.:

278

Cov.:

AF XY:

0.0528

AC XY:

3931

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0141

Gnomad4 AMR

AF:

0.0692

Gnomad4 ASJ

AF:

0.0908

Gnomad4 EAS

AF:

0.0699

Gnomad4 SAS

AF:

0.0754

Gnomad4 FIN

AF:

0.0517

Gnomad4 NFE

AF:

0.0676

Gnomad4 OTH

AF:

0.0652

Alfa

AF:

0.0445

Hom.:

Bravo

AF:

0.0529

Asia WGS

AF:

0.0680

AC:

240

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over