Variant X-11758324-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_078629.4(MSL3):c.61G>A(p.Glu21Lys) variant causes a missense 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: 21)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

MSL3
NM_078629.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.49

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSL3	NM_078629.4 link	c.61G>A	p.Glu21Lys	missense_variant	1/13	ENST00000312196.10	NP_523353.2	Q8N5Y2-1
MSL3	NM_078628.2 link	c.61G>A	p.Glu21Lys	missense_variant	1/9		NP_523352.1	Q8N5Y2-5
MSL3	NM_001282174.1 link	c.-304G>A		5_prime_UTR_variant	1/12		NP_001269103.1	Q8N5Y2-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSL3	ENST00000312196.10 link	c.61G>A	p.Glu21Lys	missense_variant	1/13	1	NM_078629.4	ENSP00000312244.4		Q8N5Y2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1025787

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

326539

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MSL3-related disorder

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 16, 2023

The MSL3 c.61G>A variant is predicted to result in the amino acid substitution p.Glu21Lys. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Uncertain

0.012

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.27

T;.;.;.

FATHMM_MKL

Benign

0.65

LIST_S2

Uncertain

0.92

D;D;D;D

M_CAP

Pathogenic

0.78

MetaRNN

Uncertain

0.63

D;D;D;D

MetaSVM

Benign

-0.46

MutationAssessor

Uncertain

2.3

M;M;.;.

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-2.4

N;D;.;.

REVEL

Uncertain

0.38

Sift

Uncertain

0.0060

D;D;.;.

Sift4G

Uncertain

0.012

D;D;.;.

Polyphen

1.0

D;.;.;.

Vest4

0.58

MutPred

0.64

Gain of methylation at E21 (P = 0.0011);Gain of methylation at E21 (P = 0.0011);Gain of methylation at E21 (P = 0.0011);Gain of methylation at E21 (P = 0.0011);

MVP

0.42

MPC

1.7

ClinPred

0.98

GERP RS

3.0

Varity_R

0.68

gMVP

0.97

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over