X-11762130-AAAG-A

Variant names:

• chrX-11762130-AAAG-A
• rs2147244252
• NM_078629.4:c.472_474delGAA

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_078629.4(MSL3):​c.472_474delGAA​(p.Glu158del) variant causes a conservative inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: MSL3 NM_078629.4 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.60
• Publications: 0 publications found

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]

MSL3 Gene-Disease associations (from GenCC):

• Basilicata-Akhtar syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_078629.4. Strenght limited to Supporting due to length of the change: 1aa.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_078629.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSL3	NM_078629.4	MANE Select	c.472_474delGAA	p.Glu158del	conservative_inframe_deletion	Exon 6 of 13	NP_523353.2	Q8N5Y2-1
	MSL3	NM_001193270.2		c.436_438delGAA	p.Glu146del	conservative_inframe_deletion	Exon 6 of 13	NP_001180199.1	Q8N5Y2-3
	MSL3	NM_078628.2		c.472_474delGAA	p.Glu158del	conservative_inframe_deletion	Exon 6 of 9	NP_523352.1	Q8N5Y2-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSL3	ENST00000312196.10	TSL:1 MANE Select	c.472_474delGAA	p.Glu158del	conservative_inframe_deletion	Exon 6 of 13	ENSP00000312244.4	Q8N5Y2-1
	MSL3	ENST00000647869.1		c.472_474delGAA	p.Glu158del	conservative_inframe_deletion	Exon 6 of 13	ENSP00000497615.1	A0A3B3IT59
	MSL3	ENST00000398527.7	TSL:2	c.436_438delGAA	p.Glu146del	conservative_inframe_deletion	Exon 6 of 13	ENSP00000381538.2	Q8N5Y2-3

Frequencies

GnomAD3 genomes Cov.: 24

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 24

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2147244252; hg19: chrX-11780249;