18-33578458-C-CCCG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_030632.3(ASXL3):c.-135_-133dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.068 (229 hom., cov: 0)
  • Exomes 𝑓: 0.034 (2 hom.)
• Consequence: ASXL3 NM_030632.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.593

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 -10 ACMG points.

• BP6: Variant 18-33578458-C-CCCG is Benign according to our data. Variant chr18-33578458-C-CCCG is described in ClinVar as [Benign]. Clinvar id is 1296668.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASXL3	NM_030632.3	c.-135_-133dup		5_prime_UTR_variant	1/12	ENST00000269197.12
ASXL3	XM_005258356.2	c.-135_-133dup		5_prime_UTR_variant	1/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASXL3	ENST00000269197.12	c.-135_-133dup		5_prime_UTR_variant	1/12	5	NM_030632.3	P4
ASXL3	ENST00000681521.1	c.-135_-133dup		5_prime_UTR_variant	1/11			A2
ASXL3	ENST00000696964.1	c.-135_-133dup		5_prime_UTR_variant	1/13			A2

Frequencies

GnomAD3 genomes AF: 0.0683 AC: 5087 AN: 74488 Hom.: 229 Cov.: 0

Gnomad AFR AF: 0.0534

Gnomad AMI AF: 0.0188

Gnomad AMR AF: 0.0576

Gnomad ASJ AF: 0.0797

Gnomad EAS AF: 0.0272

Gnomad SAS AF: 0.0383

Gnomad FIN AF: 0.0987

Gnomad MID AF: 0.0435

Gnomad NFE AF: 0.0790

Gnomad OTH AF: 0.0579

GnomAD4 exome AF: 0.0339 AC: 662 AN: 19536 Hom.: 2 Cov.: 0 AF XY: 0.0307 AC XY: 395 AN XY: 12854

Gnomad4 AFR exome AF: 0.0169

Gnomad4 AMR exome AF: 0.00556

Gnomad4 ASJ exome AF: 0.0259

Gnomad4 EAS exome AF: 0.00912

Gnomad4 SAS exome AF: 0.0260

Gnomad4 FIN exome AF: 0.0676

Gnomad4 NFE exome AF: 0.0227

Gnomad4 OTH exome AF: 0.0219

GnomAD4 genome AF: 0.0683 AC: 5087 AN: 74466 Hom.: 229 Cov.: 0 AF XY: 0.0679 AC XY: 2400 AN XY: 35370

Gnomad4 AFR AF: 0.0536

Gnomad4 AMR AF: 0.0575

Gnomad4 ASJ AF: 0.0797

Gnomad4 EAS AF: 0.0273

Gnomad4 SAS AF: 0.0388

Gnomad4 FIN AF: 0.0987

Gnomad4 NFE AF: 0.0790

Gnomad4 OTH AF: 0.0576

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

Sep 15, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs552419485; hg19: chr18-31158422;