17-40133050-T-G

Variant summary

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

The NM_001365919.1(MSL1):c.1497T>G(p.Asp499Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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)
• Consequence: MSL1 NM_001365919.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.183

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]

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=0.19842708).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSL1	NM_001365919.1	c.1497T>G	p.Asp499Glu	missense_variant	6/9	ENST00000398532.9
MSL1	NM_001365920.1	c.1449T>G	p.Asp483Glu	missense_variant	5/8
MSL1	NM_001012241.2	c.708T>G	p.Asp236Glu	missense_variant	7/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSL1	ENST00000398532.9	c.1497T>G	p.Asp499Glu	missense_variant	6/9	1	NM_001365919.1	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Aug 09, 2021

The c.708T>G (p.D236E) alteration is located in exon 7 (coding exon 5) of the MSL1 gene. This alteration results from a T to G substitution at nucleotide position 708, causing the aspartic acid (D) at amino acid position 236 to be replaced by a glutamic acid (E). 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	0.32
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
Cadd	Benign	19
Dann	Benign	0.93
DEOGEN2	Benign	0.061	T;T;.
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.76	T;T;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-2.1	N;.;.
REVEL	Benign	0.18
Sift	Uncertain	0.012	D;.;.
Sift4G	Benign	0.076	T;D;D
Vest4		0.44
MutPred		0.081		Loss of stability (P = 0.0994);.;.;
MVP		0.15
MPC		0.91
ClinPred		0.47	T
GERP RS		2.3
Varity_R		0.54
gMVP		0.49

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: chr17-38289303;