3-136151716-G-A

Position:

• chr3-136151716-G-A

Variant summary

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

The NM_018133.4(MSL2):​c.1165C>T​(p.Pro389Ser) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 32)
• Consequence: MSL2 NM_018133.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.25

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=0.26322705).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSL2	NM_018133.4	c.1165C>T	p.Pro389Ser	missense_variant	2/2	ENST00000309993.3	NP_060603.2
MSL2	NM_001145417.2	c.943C>T	p.Pro315Ser	missense_variant	2/2		NP_001138889.1
MSL2	XM_005247571.4	c.943C>T	p.Pro315Ser	missense_variant	2/2		XP_005247628.1
MSL2	XM_011512949.3	c.943C>T	p.Pro315Ser	missense_variant	2/2		XP_011511251.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSL2	ENST00000309993.3	c.1165C>T	p.Pro389Ser	missense_variant	2/2	1	NM_018133.4	ENSP00000311827.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 14, 2022

The c.1165C>T (p.P389S) alteration is located in exon 2 (coding exon 2) of the MSL2 gene. This alteration results from a C to T substitution at nucleotide position 1165, causing the proline (P) at amino acid position 389 to be replaced by a serine (S). 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	Benign	0.28
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;.
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.0	M;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.21
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.047	D;T
Polyphen		0.99	D;.
Vest4		0.50
MutPred		0.28		Gain of sheet (P = 0.0221);.;
MVP		0.14
MPC		1.4
ClinPred		0.90	D
GERP RS		5.8
Varity_R		0.18
gMVP		0.45

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

Other links and lift over

dbSNP: rs1939377614; hg19: chr3-135870558;