18-33578458-CCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCG-CCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCG

Variant names:

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

Variant summary

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

The NM_030632.3(ASXL3):​c.-147_-133dupGCCGCCGCCGCCGCC 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 0.0050 (1 hom., cov: 0)
  • Exomes 𝑓: 0.00010 (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 = 0.00496 (370/74558) while in subpopulation AFR AF= 0.0162 (268/16552). AF 95% confidence interval is 0.0146. There are 1 homozygotes in gnomad4. There are 170 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 370 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASXL3	NM_030632.3	c.-147_-133dupGCCGCCGCCGCCGCC		5_prime_UTR_variant	Exon 1 of 12	ENST00000269197.12	NP_085135.1
ASXL3	XM_005258356.2	c.-147_-133dupGCCGCCGCCGCCGCC		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_-133dupGCCGCCGCCGCCGCC		5_prime_UTR_variant	Exon 1 of 12	5	NM_030632.3	ENSP00000269197.4

Frequencies

GnomAD3 genomes AF: 0.00493 AC: 368 AN: 74580 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.0161

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00394

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00335

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000406

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00137

Gnomad OTH AF: 0.00655

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000102 AC: 2 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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000168

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00496 AC: 370 AN: 74558 Hom.: 1 Cov.: 0 AF XY: 0.00480 AC XY: 170 AN XY: 35414

Gnomad4 AFR AF: 0.0162

Gnomad4 AMR AF: 0.00394

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00336

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000406

Gnomad4 NFE AF: 0.00137

Gnomad4 OTH AF: 0.00652

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;