chr18-33578458-CCCG-C

Position:

• chr18-33578458-CCCG-C

Variant summary

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

The NM_030632.3(ASXL3):​c.-135_-133del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 93,656 control chromosomes in the GnomAD database, including 13,990 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.55 (11626 hom., cov: 0)
  • Exomes 𝑓: 0.54 (2364 hom.)
• Consequence: ASXL3 NM_030632.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00300

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-CCCG-C is Benign according to our data. Variant chr18-33578458-CCCG-C is described in ClinVar as [Benign]. Clinvar id is 1296078.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.547 AC: 40637 AN: 74300 Hom.: 11639 Cov.: 0

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.515

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.558

GnomAD4 exome AF: 0.542 AC: 10496 AN: 19378 Hom.: 2364 AF XY: 0.552 AC XY: 7051 AN XY: 12762

Gnomad4 AFR exome AF: 0.585

Gnomad4 AMR exome AF: 0.653

Gnomad4 ASJ exome AF: 0.576

Gnomad4 EAS exome AF: 0.635

Gnomad4 SAS exome AF: 0.590

Gnomad4 FIN exome AF: 0.479

Gnomad4 NFE exome AF: 0.555

Gnomad4 OTH exome AF: 0.578

GnomAD4 genome AF: 0.547 AC: 40619 AN: 74278 Hom.: 11626 Cov.: 0 AF XY: 0.546 AC XY: 19257 AN XY: 35268

Gnomad4 AFR AF: 0.468

Gnomad4 AMR AF: 0.626

Gnomad4 ASJ AF: 0.608

Gnomad4 EAS AF: 0.733

Gnomad4 SAS AF: 0.580

Gnomad4 FIN AF: 0.315

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.558

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 06, 2019

- -

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;