NM_030632.3:c.-138_-133delGCCGCC

Variant names:

• chr18-33578458-CCCGCCG-C
• rs552419485
• NM_030632.3:c.-138_-133delGCCGCC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_030632.3(ASXL3):​c.-138_-133delGCCGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0201 in 92,748 control chromosomes in the GnomAD database, including 17 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.011 (10 hom., cov: 0)
  • Exomes 𝑓: 0.057 (7 hom.)
• 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.

• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASXL3	NM_030632.3	c.-138_-133delGCCGCC		5_prime_UTR_variant	Exon 1 of 12	ENST00000269197.12	NP_085135.1
ASXL3	XM_005258356.2	c.-138_-133delGCCGCC		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.-138_-133delGCCGCC		5_prime_UTR_variant	Exon 1 of 12	5	NM_030632.3	ENSP00000269197.4

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 824 AN: 74574 Hom.: 10 Cov.: 0

Gnomad AFR AF: 0.0207

Gnomad AMI AF: 0.0188

Gnomad AMR AF: 0.0121

Gnomad ASJ AF: 0.0108

Gnomad EAS AF: 0.00251

Gnomad SAS AF: 0.00863

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.0290

Gnomad NFE AF: 0.00776

Gnomad OTH AF: 0.0164

GnomAD4 exome AF: 0.0573 AC: 1042 AN: 18196 Hom.: 7 AF XY: 0.0625 AC XY: 743 AN XY: 11888

Gnomad4 AFR exome AF: 0.115

Gnomad4 AMR exome AF: 0.0247

Gnomad4 ASJ exome AF: 0.0614

Gnomad4 EAS exome AF: 0.117

Gnomad4 SAS exome AF: 0.0458

Gnomad4 FIN exome AF: 0.0204

Gnomad4 NFE exome AF: 0.0711

Gnomad4 OTH exome AF: 0.0804

GnomAD4 genome AF: 0.0111 AC: 824 AN: 74552 Hom.: 10 Cov.: 0 AF XY: 0.0106 AC XY: 375 AN XY: 35408

Gnomad4 AFR AF: 0.0207

Gnomad4 AMR AF: 0.0121

Gnomad4 ASJ AF: 0.0108

Gnomad4 EAS AF: 0.00252

Gnomad4 SAS AF: 0.00873

Gnomad4 FIN AF: 0.00122

Gnomad4 NFE AF: 0.00776

Gnomad4 OTH AF: 0.0164

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;