18-33578458-CCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCG-CCCGCCGCCGCCGCCGCCG

Variant names:

• chr18-33578458-CCCGCCGCCGCCGCCG-C
• rs552419485
• NM_030632.3:c.-147_-133delGCCGCCGCCGCCGCC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_030632.3(ASXL3):​c.-147_-133delGCCGCCGCCGCCGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000509 in 19,662 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0056 (7 hom., cov: 0)
  • Exomes 𝑓: 0.00051 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ASXL3 NM_030632.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000509 (10/19662) while in subpopulation AFR AF= 0.0254 (3/118). AF 95% confidence interval is 0.00693. There are 0 homozygotes in gnomad4_exome. There are 7 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASXL3	NM_030632.3	c.-147_-133delGCCGCCGCCGCCGCC		5_prime_UTR_variant	Exon 1 of 12	ENST00000269197.12	NP_085135.1
ASXL3	XM_005258356.2	c.-147_-133delGCCGCCGCCGCCGCC		5_prime_UTR_variant	Exon 1 of 13		XP_005258413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASXL3	ENST00000269197	c.-147_-133delGCCGCCGCCGCCGCC		5_prime_UTR_variant	Exon 1 of 12	5	NM_030632.3	ENSP00000269197.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 416 AN: 74580 Hom.: 7 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00191

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00293

Gnomad SAS AF: 0.000539

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.0290

Gnomad NFE AF: 0.000356

Gnomad OTH AF: 0.00437

GnomAD4 exome AF: 0.000509 AC: 10 AN: 19662 Hom.: 0 AF XY: 0.000541 AC XY: 7 AN XY: 12946

Gnomad4 AFR exome AF: 0.0254

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000977

Gnomad4 NFE exome AF: 0.000168

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00558 AC: 416 AN: 74558 Hom.: 7 Cov.: 0 AF XY: 0.00585 AC XY: 207 AN XY: 35412

Gnomad4 AFR AF: 0.0222

Gnomad4 AMR AF: 0.00191

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00294

Gnomad4 SAS AF: 0.000546

Gnomad4 FIN AF: 0.00122

Gnomad4 NFE AF: 0.000356

Gnomad4 OTH AF: 0.00435

ClinVar

Not reported in ClinVar

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;