chr18-33644983-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_ModerateBP6_Moderate
The NM_030632.3(ASXL3):c.227C>T(p.Ser76Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000851 in 1,410,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000085 ( 0 hom. )
Consequence
ASXL3
NM_030632.3 missense
NM_030632.3 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 4.43
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 Likely_benign. Variant got -4 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.15296733).
BP6
?
Variant 18-33644983-C-T is Benign according to our data. Variant chr18-33644983-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2555562.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ASXL3 | NM_030632.3 | c.227C>T | p.Ser76Leu | missense_variant | 3/12 | ENST00000269197.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ASXL3 | ENST00000269197.12 | c.227C>T | p.Ser76Leu | missense_variant | 3/12 | 5 | NM_030632.3 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
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31
GnomAD3 exomes AF: 0.0000109 AC: 2AN: 183990Hom.: 0 AF XY: 0.0000205 AC XY: 2AN XY: 97656
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GnomAD4 exome AF: 0.00000851 AC: 12AN: 1410030Hom.: 0 Cov.: 29 AF XY: 0.0000115 AC XY: 8AN XY: 697900
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GnomAD4 genome ? Cov.: 31
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Bravo
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 02, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Benign
D;.
Sift4G
Benign
T;.
Polyphen
B;.
Vest4
MutPred
Loss of disorder (P = 0.0417);.;
MVP
MPC
ClinPred
T
GERP RS
Varity_R
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