rs1046412386

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001193270.2(MSL3):c.35C>T(p.Ala12Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000403 in 1,165,592 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., 6 hem., cov: 23)

Exomes 𝑓: 0.000025 ( 0 hom. 5 hem. )

Consequence

MSL3
NM_001193270.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0210

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: Likely_benign. The variant received -6 ACMG points.

BP6

Variant X-11758742-C-T is Benign according to our data. Variant chrX-11758742-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3211693.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 6 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001193270.2. 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.102+377C>T		intron	N/A	NP_523353.2	Q8N5Y2-1
MSL3	NM_001193270.2		c.35C>T	p.Ala12Val	missense	Exon 1 of 13	NP_001180199.1	Q8N5Y2-3
MSL3	NM_078628.2		c.102+377C>T		intron	N/A	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.102+377C>T		intron	N/A	ENSP00000312244.4	Q8N5Y2-1
MSL3	ENST00000398527.7	TSL:2	c.35C>T	p.Ala12Val	missense	Exon 1 of 13	ENSP00000381538.2	Q8N5Y2-3
MSL3	ENST00000648120.1		c.35C>T	p.Ala12Val	missense	Exon 1 of 1	ENSP00000496997.1	A0A3B3IS16

Frequencies

GnomAD3 genomes

AF:

0.000187

AC:

AN:

112402

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000323

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00167

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:

0.00

Gnomad OTH

AF:

0.00132

GnomAD2 exomes

AF:

0.0000277

AC:

AN:

108185

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000104

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:

0.000314

GnomAD4 exome

AF:

0.0000247

AC:

AN:

1053136

Hom.:

Cov.:

AF XY:

0.0000145

AC XY:

AN XY:

344540

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24903

American (AMR)

AF:

0.000395

AC:

AN:

27874

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18633

East Asian (EAS)

AF:

0.00

AC:

AN:

27094

South Asian (SAS)

AF:

0.00

AC:

AN:

49877

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36777

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4088

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

819522

Other (OTH)

AF:

0.000338

AC:

AN:

44368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

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:

0.000187

AC:

AN:

112456

Hom.:

Cov.:

AF XY:

0.000173

AC XY:

AN XY:

34622

show subpopulations

African (AFR)

AF:

0.0000323

AC:

AN:

31002

American (AMR)

AF:

0.00167

AC:

AN:

10781

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.00

AC:

AN:

3552

South Asian (SAS)

AF:

0.00

AC:

AN:

2758

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6131

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53148

Other (OTH)

AF:

0.00130

AC:

AN:

1534

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

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:

0.000423

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.95

CADD

Benign

5.7

(source)

DANN

Benign

0.95

FATHMM_MKL

Benign

0.090

LIST_S2

Benign

0.34

M_CAP

Benign

0.0049

MetaRNN

Benign

0.037

MetaSVM

Benign

-1.0

PhyloP100

-0.021

PROVEAN

Benign

-0.55

REVEL

Benign

0.036

Sift

Benign

0.58

Vest4

0.11

MutPred

0.15

Loss of disorder (P = 0.0875)

MVP

0.15

ClinPred

0.016

GERP RS

1.1

PromoterAI

0.037

Neutral

(source)

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.32

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.32

Position offset: -6

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

Publications

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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