X-11758324-G-A
Position:
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
NM_078629.4 missense
Scores
4
7
6
Clinical Significance
Conservation
PhyloP100: 5.49
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]
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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 | c.61G>A | p.Glu21Lys | missense_variant | 1/13 | ENST00000312196.10 | NP_523353.2 | |
MSL3 | NM_078628.2 | c.61G>A | p.Glu21Lys | missense_variant | 1/9 | NP_523352.1 | ||
MSL3 | NM_001282174.1 | c.-304G>A | 5_prime_UTR_variant | 1/12 | NP_001269103.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 21
GnomAD3 genomes
Cov.:
21
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1025787Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 326539
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1025787
Hom.:
Cov.:
29
AF XY:
AC XY:
0
AN XY:
326539
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 21
GnomAD4 genome
Cov.:
21
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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;.;.;.
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.;.
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;D;.;.
REVEL
Uncertain
Sift
Uncertain
D;D;.;.
Sift4G
Uncertain
D;D;.;.
Polyphen
D;.;.;.
Vest4
MutPred
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
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.