Genetic Variant ASXL1:p.Ala16Ala (chr20-32358823-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP7

The NM_015338.6(ASXL1):c.48C>A(p.Ala16Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A16A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ASXL1
NM_015338.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.780

Publications

0 publications found

Variant links:

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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Laboratory for Molecular Medicine, G2P, Illumina

ASXL1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP7

Synonymous conserved (PhyloP=0.78 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ASXL1	NM_015338.6	MANE Select	c.48C>A	p.Ala16Ala	synonymous	Exon 1 of 13	NP_056153.2
ASXL1	NM_001164603.1		c.48C>A	p.Ala16Ala	synonymous	Exon 1 of 5	NP_001158075.1	Q498B9
ASXL1	NM_001363734.1		c.-485C>A		upstream_gene	N/A	NP_001350663.1	A0A2R8Y5U1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ASXL1	ENST00000375687.10	TSL:5 MANE Select	c.48C>A	p.Ala16Ala	synonymous	Exon 1 of 13	ENSP00000364839.4	Q8IXJ9-1
ASXL1	ENST00000905973.1		c.48C>A	p.Ala16Ala	synonymous	Exon 1 of 12	ENSP00000576032.1
ASXL1	ENST00000915088.1		c.48C>A	p.Ala16Ala	synonymous	Exon 1 of 11	ENSP00000585147.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1356422

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

669016

African (AFR)

AF:

0.00

AC:

AN:

27284

American (AMR)

AF:

0.00

AC:

AN:

31798

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23636

East Asian (EAS)

AF:

0.00

AC:

AN:

31050

South Asian (SAS)

AF:

0.00

AC:

AN:

75414

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47206

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4426

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1059872

Other (OTH)

AF:

0.00

AC:

AN:

55736

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

0.78

PromoterAI

-0.13

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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