chr18-33578458-C-CCCGCCGCCG

Variant names:

• chr18-33578458-C-CCCGCCGCCG
• rs552419485
• NM_030632.3:c.-141_-133dupGCCGCCGCC

Variant summary

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

The NM_030632.3(ASXL3):​c.-141_-133dupGCCGCCGCC 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 0.013 (23 hom., cov: 0)
  • Exomes 𝑓: 0.00046 (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 = 0.0134 (996/74542) while in subpopulation AFR AF= 0.0395 (653/16544). AF 95% confidence interval is 0.037. There are 23 homozygotes in gnomad4. There are 475 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 996 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASXL3	NM_030632.3	c.-141_-133dupGCCGCCGCC		5_prime_UTR_variant	Exon 1 of 12	ENST00000269197.12	NP_085135.1
ASXL3	XM_005258356.2	c.-141_-133dupGCCGCCGCC		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.-141_-133dupGCCGCCGCC		5_prime_UTR_variant	Exon 1 of 12	5	NM_030632.3	ENSP00000269197.4

Frequencies

GnomAD3 genomes AF: 0.0133 AC: 994 AN: 74564 Hom.: 23 Cov.: 0

Gnomad AFR AF: 0.0395

Gnomad AMI AF: 0.0134

Gnomad AMR AF: 0.00525

Gnomad ASJ AF: 0.00631

Gnomad EAS AF: 0.00460

Gnomad SAS AF: 0.00593

Gnomad FIN AF: 0.00324

Gnomad MID AF: 0.00725

Gnomad NFE AF: 0.00600

Gnomad OTH AF: 0.0131

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000458 AC: 9 AN: 19662 Hom.: 0 Cov.: 0 AF XY: 0.000618 AC XY: 8 AN XY: 12946

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: 0.00278

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000421

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0134 AC: 996 AN: 74542 Hom.: 23 Cov.: 0 AF XY: 0.0134 AC XY: 475 AN XY: 35406

Gnomad4 AFR AF: 0.0395

Gnomad4 AMR AF: 0.00525

Gnomad4 ASJ AF: 0.00631

Gnomad4 EAS AF: 0.00504

Gnomad4 SAS AF: 0.00600

Gnomad4 FIN AF: 0.00324

Gnomad4 NFE AF: 0.00601

Gnomad4 OTH AF: 0.0130

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;