chrX-11762184-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_078629.4(MSL3):c.520A>G(p.Ile174Val) variant causes a missense change. The variant allele was found at a frequency of 0.000116 in 1,162,473 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 49 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.00013 ( 0 hom. 49 hem. )

Consequence

MSL3
NM_078629.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 6.02

Publications

1 publications found

Variant links:

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)

MSL3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05978009).

BP6

Variant X-11762184-A-G is Benign according to our data. Variant chrX-11762184-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 2409871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAdExome4 at 49 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MSL3	NM_078629.4	MANE Select	c.520A>G	p.Ile174Val	missense	Exon 6 of 13	NP_523353.2	Q8N5Y2-1
MSL3	NM_001193270.2		c.484A>G	p.Ile162Val	missense	Exon 6 of 13	NP_001180199.1	Q8N5Y2-3
MSL3	NM_078628.2		c.520A>G	p.Ile174Val	missense	Exon 6 of 9	NP_523352.1	Q8N5Y2-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MSL3	ENST00000312196.10	TSL:1 MANE Select	c.520A>G	p.Ile174Val	missense	Exon 6 of 13	ENSP00000312244.4	Q8N5Y2-1
MSL3	ENST00000647869.1		c.520A>G	p.Ile174Val	missense	Exon 6 of 13	ENSP00000497615.1	A0A3B3IT59
MSL3	ENST00000398527.7	TSL:2	c.484A>G	p.Ile162Val	missense	Exon 6 of 13	ENSP00000381538.2	Q8N5Y2-3

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112580

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000323

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000187

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000144

AC:

AN:

153153

AF XY:

0.000163

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000109

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000960

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000127

AC:

133

AN:

1049893

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

AN XY:

329811

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23908

American (AMR)

AF:

0.000111

AC:

AN:

27014

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18289

East Asian (EAS)

AF:

0.0000694

AC:

AN:

28814

South Asian (SAS)

AF:

0.000705

AC:

AN:

48228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40237

Middle Eastern (MID)

AF:

0.00124

AC:

AN:

4020

European-Non Finnish (NFE)

AF:

0.0000945

AC:

AN:

815079

Other (OTH)

AF:

0.000271

AC:

AN:

44304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000178

AC:

AN:

112580

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34722

show subpopulations

African (AFR)

AF:

0.0000323

AC:

AN:

30934

American (AMR)

AF:

0.00

AC:

AN:

10671

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2661

East Asian (EAS)

AF:

0.00

AC:

AN:

3625

South Asian (SAS)

AF:

0.00

AC:

AN:

2756

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6121

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.0000187

AC:

AN:

53366

Other (OTH)

AF:

0.00

AC:

AN:

1518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.000239

AC:

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

MSL3-related disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.043

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.78

M_CAP

Benign

0.050

MetaRNN

Benign

0.060

MetaSVM

Benign

-0.68

MutationAssessor

Benign

0.87

PhyloP100

6.0

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.65

REVEL

Benign

0.12

Sift

Benign

0.24

Sift4G

Benign

0.40

Polyphen

0.098

Vest4

0.18

MVP

0.77

MPC

0.56

ClinPred

0.11

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.23

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over