Variant X-11758742-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -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. 10/16 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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -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 id is 3211693.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSL3	NM_078629.4 link	c.102+377C>T		intron_variant		ENST00000312196.10	NP_523353.2	Q8N5Y2-1
MSL3	NM_001193270.2 link	c.35C>T	p.Ala12Val	missense_variant	1/13		NP_001180199.1	Q8N5Y2-3
MSL3	NM_078628.2 link	c.102+377C>T		intron_variant			NP_523352.1	Q8N5Y2-5
MSL3	NM_001282174.1 link	c.-263+377C>T		intron_variant			NP_001269103.1	Q8N5Y2-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSL3	ENST00000312196.10 link	c.102+377C>T		intron_variant		1	NM_078629.4	ENSP00000312244.4		Q8N5Y2-1

Frequencies

GnomAD3 genomes

AF:

0.000187

AC:

AN:

112402

Hom.:

Cov.:

AF XY:

0.000174

AC XY:

AN XY:

34558

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

GnomAD3 exomes

AF:

0.0000277

AC:

AN:

108185

Hom.:

AF XY:

0.00

AC XY:

AN XY:

39395

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 SAS 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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000395

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000338

GnomAD4 genome

AF:

0.000187

AC:

AN:

112456

Hom.:

Cov.:

AF XY:

0.000173

AC XY:

AN XY:

34622

show subpopulations

Gnomad4 AFR

AF:

0.0000323

Gnomad4 AMR

AF:

0.00167

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00130

Bravo

AF:

0.000423

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 22, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.95

CADD

Benign

5.7

DANN

Benign

0.95

FATHMM_MKL

Benign

0.090

LIST_S2

Benign

0.34

T;.

M_CAP

Benign

0.0049

MetaRNN

Benign

0.037

T;T

MetaSVM

Benign

-1.0

PROVEAN

Benign

-0.55

N;.

REVEL

Benign

0.036

Sift

Benign

0.58

T;.

Vest4

0.11

MutPred

0.15

Loss of disorder (P = 0.0875);Loss of disorder (P = 0.0875);

MVP

0.15

ClinPred

0.016

GERP RS

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over