chr18-33578458-C-CCCGCCG

Position:

• chr18-33578458-C-CCCGCCG

Variant summary

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

The NM_030632.3(ASXL3):​c.-138_-133dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.039 (105 hom., cov: 0)
  • Exomes 𝑓: 0.0030 (1 hom.)
• Consequence: ASXL3 NM_030632.3 5_prime_UTR
• Clinical Significance: Likely 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-CCCGCCG is Benign according to our data. Variant chr18-33578458-C-CCCGCCG is described in ClinVar as [Likely_benign]. Clinvar id is 1203880.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASXL3	NM_030632.3	c.-138_-133dup		5_prime_UTR_variant	1/12	ENST00000269197.12
ASXL3	XM_005258356.2	c.-138_-133dup		5_prime_UTR_variant	1/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASXL3	ENST00000269197.12	c.-138_-133dup		5_prime_UTR_variant	1/12	5	NM_030632.3	P4
ASXL3	ENST00000681521.1	c.-138_-133dup		5_prime_UTR_variant	1/11			A2
ASXL3	ENST00000696964.1	c.-138_-133dup		5_prime_UTR_variant	1/13			A2

Frequencies

GnomAD3 genomes AF: 0.0385 AC: 2873 AN: 74548 Hom.: 107 Cov.: 0

Gnomad AFR AF: 0.0836

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0338

Gnomad ASJ AF: 0.0185

Gnomad EAS AF: 0.0126

Gnomad SAS AF: 0.0248

Gnomad FIN AF: 0.0130

Gnomad MID AF: 0.0145

Gnomad NFE AF: 0.0256

Gnomad OTH AF: 0.0492

GnomAD4 exome AF: 0.00301 AC: 59 AN: 19628 Hom.: 1 Cov.: 0 AF XY: 0.00255 AC XY: 33 AN XY: 12922

Gnomad4 AFR exome AF: 0.00847

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0130

Gnomad4 FIN exome AF: 0.00293

Gnomad4 NFE exome AF: 0.00228

Gnomad4 OTH exome AF: 0.00182

GnomAD4 genome AF: 0.0385 AC: 2870 AN: 74526 Hom.: 105 Cov.: 0 AF XY: 0.0366 AC XY: 1297 AN XY: 35396

Gnomad4 AFR AF: 0.0834

Gnomad4 AMR AF: 0.0338

Gnomad4 ASJ AF: 0.0185

Gnomad4 EAS AF: 0.0126

Gnomad4 SAS AF: 0.0251

Gnomad4 FIN AF: 0.0130

Gnomad4 NFE AF: 0.0256

Gnomad4 OTH AF: 0.0490

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 02, 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;