chr18-33578458-C-CCCGCCGCCGCCG

Variant names:

• chr18-33578458-C-CCCGCCGCCGCCG
• rs552419485
• NM_030632.3:c.-144_-133dupGCCGCCGCCGCC

Variant summary

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

The NM_030632.3(ASXL3):​c.-144_-133dupGCCGCCGCCGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0058 (10 hom., cov: 0)
  • Exomes 𝑓: 0.00020 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ASXL3 NM_030632.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00581 (433/74554) while in subpopulation AFR AF= 0.0195 (323/16550). AF 95% confidence interval is 0.0178. There are 10 homozygotes in gnomad4. There are 194 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 433 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASXL3	NM_030632.3	c.-144_-133dupGCCGCCGCCGCC		5_prime_UTR_variant	Exon 1 of 12	ENST00000269197.12	NP_085135.1
ASXL3	XM_005258356.2	c.-144_-133dupGCCGCCGCCGCC		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.-144_-133dupGCCGCCGCCGCC		5_prime_UTR_variant	Exon 1 of 12	5	NM_030632.3	ENSP00000269197.4

Frequencies

GnomAD3 genomes AF: 0.00581 AC: 433 AN: 74574 Hom.: 10 Cov.: 0

Gnomad AFR AF: 0.0195

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00382

Gnomad ASJ AF: 0.000450

Gnomad EAS AF: 0.00335

Gnomad SAS AF: 0.000540

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00725

Gnomad NFE AF: 0.00165

Gnomad OTH AF: 0.00328

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000203 AC: 4 AN: 19662 Hom.: 0 Cov.: 0 AF XY: 0.0000772 AC XY: 1 AN XY: 12946

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000926

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000252

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00581 AC: 433 AN: 74554 Hom.: 10 Cov.: 0 AF XY: 0.00548 AC XY: 194 AN XY: 35406

Gnomad4 AFR AF: 0.0195

Gnomad4 AMR AF: 0.00382

Gnomad4 ASJ AF: 0.000450

Gnomad4 EAS AF: 0.00294

Gnomad4 SAS AF: 0.000546

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00165

Gnomad4 OTH AF: 0.00326

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;