NM_015338.6:c.54C>G

Variant names:

• chr20-32358829-C-G
• rs1241861910
• NM_015338.6:c.54C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4 BP7

The NM_015338.6(ASXL1):​c.54C>G​(p.Arg18Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R18R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ASXL1 NM_015338.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.13
• Publications: 1 publications found

Genes affected

ASXL1 (HGNC:18318): (ASXL transcriptional regulator 1) This gene is similar to the Drosophila additional sex combs gene, which encodes a chromatin-binding protein required for normal determination of segment identity in the developing embryo. The protein is a member of the Polycomb group of proteins, which are necessary for the maintenance of stable repression of homeotic and other loci. The protein is thought to disrupt chromatin in localized areas, enhancing transcription of certain genes while repressing the transcription of other genes. The protein encoded by this gene functions as a ligand-dependent co-activator for retinoic acid receptor in cooperation with nuclear receptor coactivator 1. Mutations in this gene are associated with myelodysplastic syndromes and chronic myelomonocytic leukemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

ASXL1 Gene-Disease associations (from GenCC):

• Bohring-Opitz syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Illumina, Laboratory for Molecular Medicine, Orphanet, G2P, PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.184).
• BP7: Synonymous conserved (PhyloP=2.13 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015338.6. 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
	ASXL1	NM_015338.6	MANE Select	c.54C>G	p.Arg18Arg	synonymous	Exon 1 of 13	NP_056153.2
	ASXL1	NM_001164603.1		c.54C>G	p.Arg18Arg	synonymous	Exon 1 of 5	NP_001158075.1	Q498B9
	ASXL1	NM_001363734.1		c.-479C>G		upstream_gene	N/A	NP_001350663.1	A0A2R8Y5U1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASXL1	ENST00000375687.10	TSL:5 MANE Select	c.54C>G	p.Arg18Arg	synonymous	Exon 1 of 13	ENSP00000364839.4	Q8IXJ9-1
	ASXL1	ENST00000905973.1		c.54C>G	p.Arg18Arg	synonymous	Exon 1 of 12	ENSP00000576032.1
	ASXL1	ENST00000915088.1		c.54C>G	p.Arg18Arg	synonymous	Exon 1 of 11	ENSP00000585147.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	14
DANN	Benign	0.91
PhyloP100		2.1
PromoterAI		-0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1241861910; hg19: chr20-30946632;