rs200723688
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Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The NM_030632.3(ASXL3):c.3350G>A(p.Arg1117Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000178 in 1,613,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00019 ( 0 hom. )
Consequence
ASXL3
NM_030632.3 missense
NM_030632.3 missense
Scores
2
6
11
Clinical Significance
Conservation
PhyloP100: 4.72
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -18 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.2126365).
BP6
Variant 18-33743198-G-A is Benign according to our data. Variant chr18-33743198-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 377254.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.000188 (275/1461680) while in subpopulation NFE AF= 0.000235 (261/1111864). AF 95% confidence interval is 0.000211. There are 0 homozygotes in gnomad4_exome. There are 130 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 12 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ASXL3 | NM_030632.3 | c.3350G>A | p.Arg1117Gln | missense_variant | 12/12 | ENST00000269197.12 | |
LOC124904347 | XR_007066447.1 | n.177C>T | non_coding_transcript_exon_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ASXL3 | ENST00000269197.12 | c.3350G>A | p.Arg1117Gln | missense_variant | 12/12 | 5 | NM_030632.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000789 AC: 12AN: 152116Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000723 AC: 18AN: 248958Hom.: 0 AF XY: 0.0000740 AC XY: 10AN XY: 135114
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GnomAD4 exome AF: 0.000188 AC: 275AN: 1461680Hom.: 0 Cov.: 33 AF XY: 0.000179 AC XY: 130AN XY: 727120
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GnomAD4 genome AF: 0.0000788 AC: 12AN: 152234Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74454
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 15, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | ASXL3: BP4 - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Nov 02, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Uncertain
D;.
Sift4G
Uncertain
D;.
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at