18-33578269-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_030632.3(ASXL3):c.-363C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0646 in 149,198 control chromosomes in the GnomAD database, including 1,065 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.065 (1065 hom., cov: 31)
  • Exomes 𝑓: 0.033 (0 hom.)
• Consequence: ASXL3 NM_030632.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.92

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 18-33578269-C-A is Benign according to our data. Variant chr18-33578269-C-A is described in ClinVar as [Benign]. Clinvar id is 1249512.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASXL3	NM_030632.3	c.-363C>A		5_prime_UTR_variant	1/12	ENST00000269197.12
ASXL3	XM_005258356.2	c.-363C>A		5_prime_UTR_variant	1/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASXL3	ENST00000269197.12	c.-363C>A		5_prime_UTR_variant	1/12	5	NM_030632.3	P4
ASXL3	ENST00000681521.1	c.-363C>A		5_prime_UTR_variant	1/11			A2
ASXL3	ENST00000696964.1	c.-363C>A		5_prime_UTR_variant	1/13			A2

Frequencies

GnomAD3 genomes AF: 0.0645 AC: 9623 AN: 149110 Hom.: 1063 Cov.: 31

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0258

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000396

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.000837

Gnomad MID AF: 0.0229

Gnomad NFE AF: 0.000775

Gnomad OTH AF: 0.0474

GnomAD4 exome AF: 0.0333 AC: 1 AN: 30 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 22

Gnomad4 AFR exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0646 AC: 9638 AN: 149168 Hom.: 1065 Cov.: 31 AF XY: 0.0610 AC XY: 4435 AN XY: 72720

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.0258

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000596

Gnomad4 SAS AF: 0.000417

Gnomad4 FIN AF: 0.000837

Gnomad4 NFE AF: 0.000775

Gnomad4 OTH AF: 0.0470

Alfa AF: 0.0515 Hom.: 83

Bravo AF: 0.0741

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 13, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	18
Dann	Benign	0.86

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs141022157; hg19: chr18-31158233;