Variant chrX-11760922-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_078629.4(MSL3):c.367G>C(p.Glu123Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000056 in 1,071,859 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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 Uncertain significance (★★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0000056 ( 0 hom. 3 hem. )

Consequence

MSL3
NM_078629.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 1.99

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.

BP4

Computational evidence support a benign effect (MetaRNN=0.11648372).

BS2

High Hemizygotes in GnomAdExome4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSL3	NM_078629.4 linkuse as main transcript	c.367G>C	p.Glu123Gln	missense_variant	4/13	ENST00000312196.10	NP_523353.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSL3	ENST00000312196.10 linkuse as main transcript	c.367G>C	p.Glu123Gln	missense_variant	4/13	1	NM_078629.4	ENSP00000312244	P4	Q8N5Y2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000560

AC:

AN:

1071859

Hom.:

Cov.:

AF XY:

0.00000879

AC XY:

AN XY:

341119

show subpopulations

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:

0.0000198

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000364

Gnomad4 OTH exome

AF:

0.0000222

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

Sep 29, 2021

PM2 -

Basilicata-Akhtar syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Jan 28, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.028

T;.;.;.;.

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.75

T;T;T;T;T

M_CAP

Benign

0.0038

MetaRNN

Benign

0.12

T;T;T;T;T

MetaSVM

Benign

-0.92

MutationTaster

Benign

1.0

D;N;N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.53

N;N;.;.;N

REVEL

Benign

0.020

Sift

Benign

0.14

T;T;.;.;T

Sift4G

Benign

0.41

T;T;.;.;T

Polyphen

0.041

B;.;.;.;.

Vest4

0.089

MutPred

0.27

Loss of solvent accessibility (P = 0.0174);Loss of solvent accessibility (P = 0.0174);Loss of solvent accessibility (P = 0.0174);Loss of solvent accessibility (P = 0.0174);.;

MVP

0.26

MPC

0.61

ClinPred

0.49

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.089

gMVP

0.19

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