3-136151532-T-C

Position:

• chr3-136151532-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000309993.3(MSL2):​c.1349A>G​(p.Lys450Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MSL2 ENST00000309993.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.83

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14179876).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSL2	NM_018133.4	c.1349A>G	p.Lys450Arg	missense_variant	2/2	ENST00000309993.3	NP_060603.2
MSL2	NM_001145417.2	c.1127A>G	p.Lys376Arg	missense_variant	2/2		NP_001138889.1
MSL2	XM_005247571.4	c.1127A>G	p.Lys376Arg	missense_variant	2/2		XP_005247628.1
MSL2	XM_011512949.3	c.1127A>G	p.Lys376Arg	missense_variant	2/2		XP_011511251.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSL2	ENST00000309993.3	c.1349A>G	p.Lys450Arg	missense_variant	2/2	1	NM_018133.4	ENSP00000311827	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Feb 20, 2024

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Variants in candidate genes are classified as variants of uncertain significance in accordance with ACMG guidelines (PMID: 25741868) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	T;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.0	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.082
Sift	Benign	0.22	T;T
Sift4G	Benign	0.20	T;T
Polyphen		0.87	P;.
Vest4		0.073
MutPred		0.21		Loss of methylation at K450 (P = 0.0067);.;
MVP		0.043
MPC		1.2
ClinPred		0.78	D
GERP RS		4.7
Varity_R		0.15
gMVP		0.71

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: chr3-135870374;