rs1555906707
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP5_ModerateBP4
The NM_078629.4(MSL3):c.923T>C(p.Leu308Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 23)
Consequence
MSL3
NM_078629.4 missense
NM_078629.4 missense
Scores
3
12
Clinical Significance
Conservation
PhyloP100: 5.02
Genes affected
MSL3 (HGNC:7370): (MSL complex subunit 3) This gene encodes a nuclear protein that is similar to the product of the Drosophila male-specific lethal-3 gene. The Drosophila protein plays a critical role in a dosage-compensation pathway, which equalizes X-linked gene expression in males and females. Thus, the human protein is thought to play a similar function in chromatin remodeling and transcriptional regulation, and it has been found as part of a complex that is responsible for histone H4 lysine-16 acetylation. This gene can undergo X inactivation. Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 2, 7 and 8. [provided by RefSeq, Jul 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-11765481-T-C is Pathogenic according to our data. Variant chrX-11765481-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 487567.Status of the report is criteria_provided_single_submitter, 1 stars.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.25802967). . Strength limited to SUPPORTING due to the PP5.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MSL3 | NM_078629.4 | c.923T>C | p.Leu308Pro | missense_variant | 9/13 | ENST00000312196.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MSL3 | ENST00000312196.10 | c.923T>C | p.Leu308Pro | missense_variant | 9/13 | 1 | NM_078629.4 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Intellectual disability Pathogenic:1
Likely pathogenic, criteria provided, single submitter | research | Equipe Genetique des Anomalies du Developpement, Université de Bourgogne | Jan 01, 2017 | - - |
Basilicata-Akhtar syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 05, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T;T;T;.;.;.;.;.;T;.;T;T;.;.;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;.;.;N;.;.;.;.;.;.;.;.;.;.;.;.
REVEL
Benign
Sift
Benign
T;T;T;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.
Sift4G
Benign
T;T;T;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.
Polyphen
0.0060
.;B;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Vest4
MutPred
0.46
.;Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);.;Gain of relative solvent accessibility (P = 0.005);.;.;.;.;.;.;.;.;.;.;.;.;.;
MVP
MPC
1.1
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at