Variant 18-33607742-G-A 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.137+66G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,198,630 control chromosomes in the GnomAD database, including 14,583 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3162 hom., cov: 32)

Exomes 𝑓: 0.14 ( 11421 hom. )

Consequence

ASXL3
NM_030632.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.402

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 18-33607742-G-A is Benign according to our data. Variant chr18-33607742-G-A is described in ClinVar as [Benign]. Clinvar id is 1273037.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.305 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.137+66G>A		intron_variant		ENST00000269197.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASXL3	ENST00000269197.12 linkuse as main transcript	c.137+66G>A		intron_variant		5	NM_030632.3	P4	Q9C0F0-1

Frequencies

GnomAD3 genomes

AF:

0.186

AC:

28270

AN:

151722

Hom.:

3152

Cov.:

show subpopulations

Gnomad AFR

AF:

0.310

Gnomad AMI

AF:

0.205

Gnomad AMR

AF:

0.168

Gnomad ASJ

AF:

0.169

Gnomad EAS

AF:

0.133

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.125

Gnomad MID

AF:

0.105

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.170

GnomAD4 exome

AF:

0.143

AC:

149784

AN:

1046790

Hom.:

11421

AF XY:

0.142

AC XY:

75218

AN XY:

530274

show subpopulations

Gnomad4 AFR exome

AF:

0.319

Gnomad4 AMR exome

AF:

0.149

Gnomad4 ASJ exome

AF:

0.171

Gnomad4 EAS exome

AF:

0.167

Gnomad4 SAS exome

AF:

0.123

Gnomad4 FIN exome

AF:

0.120

Gnomad4 NFE exome

AF:

0.138

Gnomad4 OTH exome

AF:

0.153

GnomAD4 genome

AF:

0.186

AC:

28318

AN:

151840

Hom.:

3162

Cov.:

AF XY:

0.184

AC XY:

13671

AN XY:

74196

show subpopulations

Gnomad4 AFR

AF:

0.310

Gnomad4 AMR

AF:

0.167

Gnomad4 ASJ

AF:

0.169

Gnomad4 EAS

AF:

0.133

Gnomad4 SAS

AF:

0.121

Gnomad4 FIN

AF:

0.125

Gnomad4 NFE

AF:

0.135

Gnomad4 OTH

AF:

0.168

Alfa

AF:

0.140

Hom.:

2736

Bravo

AF:

0.196

Asia WGS

AF:

0.139

AC:

487

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	Jul 03, 2018	- -

Severe feeding difficulties-failure to thrive-microcephaly due to ASXL3 deficiency syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.2

DANN

Benign

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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