NM_078629.4:c.358G>A

Variant names:

• chrX-11760913-G-A
• rs762777627
• NM_078629.4:c.358G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_078629.4(MSL3):​c.358G>A​(p.Glu120Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000269 in 1,079,091 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.000027 (0 hom. 7 hem.)
• Consequence: MSL3 NM_078629.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 4.73
• 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: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.081608206).
• BP6: Variant X-11760913-G-A is Benign according to our data. Variant chrX-11760913-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3037087.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 7 XL gene

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.358G>A	p.Glu120Lys	missense	Exon 4 of 13	NP_523353.2	Q8N5Y2-1
	MSL3	NM_001193270.2		c.322G>A	p.Glu108Lys	missense	Exon 4 of 13	NP_001180199.1	Q8N5Y2-3
	MSL3	NM_078628.2		c.358G>A	p.Glu120Lys	missense	Exon 4 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.358G>A	p.Glu120Lys	missense	Exon 4 of 13	ENSP00000312244.4	Q8N5Y2-1
	MSL3	ENST00000647869.1		c.358G>A	p.Glu120Lys	missense	Exon 4 of 13	ENSP00000497615.1	A0A3B3IT59
	MSL3	ENST00000398527.7	TSL:2	c.322G>A	p.Glu108Lys	missense	Exon 4 of 13	ENSP00000381538.2	Q8N5Y2-3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD2 exomes AF: 0.000148 AC: 23 AN: 155134 AF XY: 0.000133

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000904

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000254

GnomAD4 exome AF: 0.0000269 AC: 29 AN: 1079091 Hom.: 0 Cov.: 27 AF XY: 0.0000202 AC XY: 7 AN XY: 347299

African (AFR) AF: 0.00 AC: 0 AN: 25897

American (AMR) AF: 0.000833 AC: 28 AN: 33607

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18999

East Asian (EAS) AF: 0.00 AC: 0 AN: 29720

South Asian (SAS) AF: 0.00 AC: 0 AN: 51126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39778

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4098

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 830583

Other (OTH) AF: 0.0000221 AC: 1 AN: 45283

GnomAD4 genome Cov.: 24

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.0000580 AC: 7

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Inborn genetic diseases (1)
-	-	1	MSL3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.56
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.018	T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.7
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.083
Sift	Benign	0.24	T
Sift4G	Benign	0.18	T
Polyphen		0.60	P
Vest4		0.20
MutPred		0.37		Gain of ubiquitination at E120 (P = 0.0048)
MVP		0.29
MPC		0.75
ClinPred		0.035	T
GERP RS		4.6
Varity_R		0.30
gMVP		0.41
Mutation Taster		=295/5	polymorphism

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

Other links and lift over

dbSNP: rs762777627; hg19: chrX-11779032;