NM_015338.6:c.3759T>C

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015338.6(ASXL1):c.3759T>C(p.Ser1253Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 1,613,818 control chromosomes in the GnomAD database, including 127,377 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 10527 hom., cov: 33)

Exomes 𝑓: 0.39 ( 116850 hom. )

Consequence

ASXL1
NM_015338.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.429

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 20-32436471-T-C is Benign according to our data. Variant chr20-32436471-T-C is described in ClinVar as [Benign]. Clinvar id is 338113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-32436471-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.429 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASXL1	NM_015338.6 link	c.3759T>C	p.Ser1253Ser	synonymous_variant	Exon 13 of 13	ENST00000375687.10	NP_056153.2	Q8IXJ9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASXL1	ENST00000375687.10 link	c.3759T>C	p.Ser1253Ser	synonymous_variant	Exon 13 of 13	5	NM_015338.6	ENSP00000364839.4		Q8IXJ9-1

Frequencies

GnomAD3 genomes

AF:

0.352

AC:

53576

AN:

151994

Hom.:

10515

Cov.:

show subpopulations

Gnomad AFR

AF:

0.198

Gnomad AMI

AF:

0.454

Gnomad AMR

AF:

0.396

Gnomad ASJ

AF:

0.320

Gnomad EAS

AF:

0.737

Gnomad SAS

AF:

0.429

Gnomad FIN

AF:

0.467

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.385

Gnomad OTH

AF:

0.347

GnomAD3 exomes

AF:

0.424

AC:

106546

AN:

251140

Hom.:

24465

AF XY:

0.422

AC XY:

57225

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.196

Gnomad AMR exome

AF:

0.481

Gnomad ASJ exome

AF:

0.326

Gnomad EAS exome

AF:

0.774

Gnomad SAS exome

AF:

0.407

Gnomad FIN exome

AF:

0.469

Gnomad NFE exome

AF:

0.389

Gnomad OTH exome

AF:

0.392

GnomAD4 exome

AF:

0.393

AC:

574814

AN:

1461706

Hom.:

116850

Cov.:

AF XY:

0.392

AC XY:

285353

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.193

Gnomad4 AMR exome

AF:

0.471

Gnomad4 ASJ exome

AF:

0.329

Gnomad4 EAS exome

AF:

0.722

Gnomad4 SAS exome

AF:

0.413

Gnomad4 FIN exome

AF:

0.472

Gnomad4 NFE exome

AF:

0.381

Gnomad4 OTH exome

AF:

0.388

GnomAD4 genome

AF:

0.352

AC:

53608

AN:

152112

Hom.:

10527

Cov.:

AF XY:

0.360

AC XY:

26782

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.198

Gnomad4 AMR

AF:

0.396

Gnomad4 ASJ

AF:

0.320

Gnomad4 EAS

AF:

0.738

Gnomad4 SAS

AF:

0.430

Gnomad4 FIN

AF:

0.467

Gnomad4 NFE

AF:

0.385

Gnomad4 OTH

AF:

0.345

Alfa

AF:

0.365

Hom.:

7342

Bravo

AF:

0.346

Asia WGS

AF:

0.492

AC:

1710

AN:

3478

EpiCase

AF:

0.362

EpiControl

AF:

0.367

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 07, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Bohring-Opitz syndrome

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.2

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over