18-33578991-C-T

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.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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.840

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=-0.68).
• 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_single_submitter, 1 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	c.54+306C>T		intron_variant		ENST00000269197.12
ASXL3	XM_005258356.2	c.54+306C>T		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0527 AC: 8026 AN: 152182 Hom.: 279 Cov.: 32

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.: 61 Cov.: 0 AF XY: 0.0739 AC XY: 909 AN XY: 12308

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.: 32 AF XY: 0.0528 AC XY: 3931 AN XY: 74486

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.: 55

Bravo AF: 0.0529

Asia WGS AF: 0.0680 AC: 240 AN: 3478

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

Aug 10, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	15
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

Other links and lift over

dbSNP: rs116955773; hg19: chr18-31158955;