Variant 3-136151244-A-G 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_018133.4(MSL2):c.1637T>C(p.Ile546Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000294 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

MSL2
NM_018133.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.73

Variant links:

Genes affected

MSL2 (HGNC:25544): (MSL complex subunit 2) Predicted to enable ubiquitin protein ligase activity. Involved in histone H4-K16 acetylation. Part of MSL complex. [provided by Alliance of Genome Resources, Apr 2022]

MSL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.112624496).

BS2

High AC in GnomAdExome4 at 43 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSL2	NM_018133.4 linkuse as main transcript	c.1637T>C	p.Ile546Thr	missense_variant	2/2	ENST00000309993.3	NP_060603.2	Q9HCI7-1
MSL2	NM_001145417.2 linkuse as main transcript	c.1415T>C	p.Ile472Thr	missense_variant	2/2		NP_001138889.1	Q9HCI7-2
MSL2	XM_005247571.4 linkuse as main transcript	c.1415T>C	p.Ile472Thr	missense_variant	2/2		XP_005247628.1	Q9HCI7-2
MSL2	XM_011512949.3 linkuse as main transcript	c.1415T>C	p.Ile472Thr	missense_variant	2/2		XP_011511251.1	Q9HCI7-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSL2	ENST00000309993.3 linkuse as main transcript	c.1637T>C	p.Ile546Thr	missense_variant	2/2	1	NM_018133.4	ENSP00000311827.2		Q9HCI7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251408

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

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:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000294

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727248

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000387

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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 submitter

clinical testing

Ambry Genetics

Jan 22, 2024

The c.1637T>C (p.I546T) alteration is located in exon 2 (coding exon 2) of the MSL2 gene. This alteration results from a T to C substitution at nucleotide position 1637, causing the isoleucine (I) at amino acid position 546 to be replaced by a threonine (T). 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

0.85

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.035

T;.

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;.

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

0.030

N;N

REVEL

Benign

0.22

Sift

Benign

0.50

T;T

Sift4G

Benign

0.70

T;T

Polyphen

0.025

B;.

Vest4

0.47

MVP

0.043

MPC

0.62

ClinPred

0.030

GERP RS

3.5

Varity_R

0.042

gMVP

0.75

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

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