rs1555907653

Variant names:

• chrX-11772674-G-GC
• rs1555907653
• NM_078629.4:c.1436dupC

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Moderate PM2 PP5_Moderate

The NM_078629.4(MSL3):​c.1436dupC​(p.Leu480PhefsTer6) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: MSL3 NM_078629.4 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 6.87

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0824 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-11772674-G-GC is Pathogenic according to our data. Variant chrX-11772674-G-GC is described in ClinVar as [Likely_pathogenic]. Clinvar id is 487571.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSL3	NM_078629.4	c.1436dupC	p.Leu480PhefsTer6	frameshift_variant	Exon 12 of 13	ENST00000312196.10	NP_523353.2
MSL3	NM_001193270.2	c.1400dupC	p.Leu468PhefsTer6	frameshift_variant	Exon 12 of 13		NP_001180199.1
MSL3	NM_001282174.1	c.989dupC	p.Leu331PhefsTer6	frameshift_variant	Exon 11 of 12		NP_001269103.1
MSL3	NM_006800.4	c.938dupC	p.Leu314PhefsTer6	frameshift_variant	Exon 11 of 12		NP_006791.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSL3	ENST00000312196.10	c.1436dupC	p.Leu480PhefsTer6	frameshift_variant	Exon 12 of 13	1	NM_078629.4	ENSP00000312244.4

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 24

GnomAD4 genome Cov.: 24

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual disability Pathogenic:1

Jan 01, 2017

Equipe Genetique des Anomalies du Developpement, Université de Bourgogne

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1555907653; hg19: chrX-11790793;