Variant 17-40129515-A-T 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_001365919.1(MSL1):c.1263A>T(p.Glu421Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,613,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

MSL1
NM_001365919.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.08

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]

MSL1 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=0.08823004).

BS2

High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSL1	NM_001365919.1 linkuse as main transcript	c.1263A>T	p.Glu421Asp	missense_variant	3/9	ENST00000398532.9	NP_001352848.1
MSL1	NM_001365920.1 linkuse as main transcript	c.1263A>T	p.Glu421Asp	missense_variant	3/8		NP_001352849.1
MSL1	NM_001365921.2 linkuse as main transcript	c.1263A>T	p.Glu421Asp	missense_variant	3/3		NP_001352850.1
MSL1	NM_001012241.2 linkuse as main transcript	c.474A>T	p.Glu158Asp	missense_variant	4/10		NP_001012241.1	Q68DK7-3B3KWR7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSL1	ENST00000398532.9 linkuse as main transcript	c.1263A>T	p.Glu421Asp	missense_variant	3/9	1	NM_001365919.1	ENSP00000381543.3		Q68DK7-1

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249044

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135178

show subpopulations

Gnomad AFR exome

AF:

0.0000647

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000233

AC:

AN:

1461698

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727132

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:

0.0000306

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000592

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.0000567

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

Oct 22, 2024

The c.474A>T (p.E158D) alteration is located in exon 4 (coding exon 2) of the MSL1 gene. This alteration results from a A to T substitution at nucleotide position 474, causing the glutamic acid (E) at amino acid position 158 to be replaced by an aspartic acid (D). 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

0.088

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Benign

0.91

DEOGEN2

Benign

0.033

T;T;T;.

Eigen

Benign

-0.12

Eigen_PC

Benign

0.091

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.79

T;T;T;T

M_CAP

Benign

0.0014

MetaRNN

Benign

0.088

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.83

L;.;.;.

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.74

N;.;.;.

REVEL

Benign

0.067

Sift

Benign

0.089

T;.;.;.

Sift4G

Benign

0.47

T;T;T;T

Polyphen

0.040

B;.;.;.

Vest4

0.087

MutPred

0.24

Gain of loop (P = 0.0502);Gain of loop (P = 0.0502);Gain of loop (P = 0.0502);.;

MVP

0.10

MPC

0.59

ClinPred

0.081

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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