rs1555907623
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_078629.4(MSL3):c.1374_1381del(p.Leu459GlufsTer13) variant causes a frameshift, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 22)
Consequence
MSL3
NM_078629.4 frameshift, splice_region
NM_078629.4 frameshift, splice_region
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.87
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 Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-11772246-CGATTGTTT-C is Pathogenic according to our data. Variant chrX-11772246-CGATTGTTT-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 487565.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MSL3 | NM_078629.4 | c.1374_1381del | p.Leu459GlufsTer13 | frameshift_variant, splice_region_variant | 11/13 | ENST00000312196.10 | |
MSL3 | NM_001193270.2 | c.1338_1345del | p.Leu447GlufsTer13 | frameshift_variant, splice_region_variant | 11/13 | ||
MSL3 | NM_001282174.1 | c.927_934del | p.Leu310GlufsTer13 | frameshift_variant, splice_region_variant | 10/12 | ||
MSL3 | NM_006800.4 | c.876_883del | p.Leu293GlufsTer13 | frameshift_variant, splice_region_variant | 10/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MSL3 | ENST00000312196.10 | c.1374_1381del | p.Leu459GlufsTer13 | frameshift_variant, splice_region_variant | 11/13 | 1 | NM_078629.4 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD3 genomes
?
Cov.:
22
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 22
GnomAD4 genome
?
Cov.:
22
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 | Dec 12, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at