Genetic Variant NM_030632.3:c.-165_-133delGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCC (chr18-33578458-CCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCG-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_030632.3(ASXL3):c.-165_-133delGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 0)

Consequence

ASXL3
NM_030632.3 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.218

Publications

1 publications found

Variant links:

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]

ASXL3 Gene-Disease associations (from GenCC):

severe feeding difficulties-failure to thrive-microcephaly due to ASXL3 deficiency syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae), Illumina
syndromic intellectual disability
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ASXL3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030632.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASXL3	NM_030632.3	MANE Select	c.-165_-133delGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCC		5_prime_UTR	Exon 1 of 12	NP_085135.1	Q9C0F0-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ASXL3	ENST00000269197.12	TSL:5 MANE Select	c.-165_-133delGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCC	5_prime_UTR	Exon 1 of 12	ENSP00000269197.4	Q9C0F0-1
ASXL3	ENST00000696964.1		c.-165_-133delGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCC	5_prime_UTR	Exon 1 of 13	ENSP00000513003.1	A0A8V8TKV8
ASXL3	ENST00000681521.1		c.-165_-133delGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCC	5_prime_UTR	Exon 1 of 11	ENSP00000506037.1	A0A7P0TAE5

Frequencies

GnomAD3 genomes

AF:

0.0000134

AC:

AN:

74588

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000605

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0000134

AC:

AN:

74588

Hom.:

Cov.:

AF XY:

0.0000282

AC XY:

AN XY:

35418

show subpopulations

African (AFR)

AF:

0.0000605

AC:

AN:

16534

American (AMR)

AF:

0.00

AC:

AN:

8376

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2220

East Asian (EAS)

AF:

0.00

AC:

AN:

2390

South Asian (SAS)

AF:

0.00

AC:

AN:

1854

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2466

Middle Eastern (MID)

AF:

0.00

AC:

AN:

138

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

39320

Other (OTH)

AF:

0.00

AC:

AN:

916

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.22

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over