rs1555906768
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_078629.4(MSL3):c.1036C>T(p.Gln346Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 24)
Consequence
MSL3
NM_078629.4 stop_gained
NM_078629.4 stop_gained
Scores
2
2
1
Clinical Significance
Conservation
PhyloP100: 6.49
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 18 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-11765594-C-T is Pathogenic according to our data. Variant chrX-11765594-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 487566.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-11765594-C-T is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MSL3 | NM_078629.4 | c.1036C>T | p.Gln346Ter | stop_gained | 9/13 | ENST00000312196.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MSL3 | ENST00000312196.10 | c.1036C>T | p.Gln346Ter | stop_gained | 9/13 | 1 | NM_078629.4 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 24
GnomAD3 genomes
?
Cov.:
24
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 24
GnomAD4 genome
?
Cov.:
24
ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Aug 24, 2022 | Nonsense variant predicted to result in protein truncation, as the last 176 amino acids are lost, and other loss-of-function variants have been reported downstream in HGMD and the published literature (Stenson et al., 2014; Basilicata et al., 2018); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 30224647) - |
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
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A;A;A;D
Vest4
GERP RS
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