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GeneBe

17-40133103-G-T

Variant summary

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

The NM_001365919.1(MSL1):c.1550G>T(p.Arg517Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

MSL1
NM_001365919.1 missense

Scores

8
7
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.59
Variant links:
Genes affected
MSL1 (HGNC:27905): (MSL complex subunit 1) Predicted to enable chromatin binding activity. Involved in histone H4-K16 acetylation. Located in nucleoplasm. Part of MSL complex. [provided by Alliance of Genome Resources, Apr 2022]

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 UniProt
MSL1NM_001365919.1 linkuse as main transcriptc.1550G>T p.Arg517Met missense_variant 6/9 ENST00000398532.9
MSL1NM_001365920.1 linkuse as main transcriptc.1502G>T p.Arg501Met missense_variant 5/8
MSL1NM_001012241.2 linkuse as main transcriptc.761G>T p.Arg254Met missense_variant 7/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MSL1ENST00000398532.9 linkuse as main transcriptc.1550G>T p.Arg517Met missense_variant 6/91 NM_001365919.1 P3Q68DK7-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1455472
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
723296
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.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 28, 2024The c.761G>T (p.R254M) alteration is located in exon 7 (coding exon 5) of the MSL1 gene. This alteration results from a G to T substitution at nucleotide position 761, causing the arginine (R) at amino acid position 254 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.35
D
BayesDel_noAF
Pathogenic
0.26
Cadd
Pathogenic
31
Dann
Benign
0.88
DEOGEN2
Benign
0.40
T;T;.
Eigen
Uncertain
0.62
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.95
D;D;D
M_CAP
Uncertain
0.11
D
MetaRNN
Uncertain
0.43
T;T;T
MetaSVM
Benign
-0.36
T
MutationAssessor
Uncertain
2.6
M;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.92
D
PROVEAN
Pathogenic
-5.2
D;.;.
REVEL
Uncertain
0.47
Sift
Pathogenic
0.0
D;.;.
Sift4G
Uncertain
0.0020
D;D;D
Vest4
0.70
MutPred
0.36
Loss of methylation at K518 (P = 0.0273);.;.;
MVP
0.33
MPC
1.7
ClinPred
0.99
D
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.9
Varity_R
0.82
gMVP
0.93

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.

Other links and lift over

hg19: chr17-38289356; API