Variant 17-40134314-G-A 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.1790G>A(p.Arg597Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000642 in 1,557,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

MSL1
NM_001365919.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.42

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:

MSL1 (HGNC:):

MSL1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.25778002).

BS2

High AC in GnomAdExome4 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.1790G>A	p.Arg597Gln	missense_variant	9/9	ENST00000398532.9	NP_001352848.1
MSL1	NM_001365920.1 linkuse as main transcript	c.1742G>A	p.Arg581Gln	missense_variant	8/8		NP_001352849.1
MSL1	NM_001012241.2 linkuse as main transcript	c.1001G>A	p.Arg334Gln	missense_variant	10/10		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.1790G>A	p.Arg597Gln	missense_variant	9/9	1	NM_001365919.1	ENSP00000381543.3		Q68DK7-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000640

AC:

AN:

1405460

Hom.:

Cov.:

AF XY:

0.00000721

AC XY:

AN XY:

693812

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:

0.00000832

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

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

Nov 27, 2023

The c.1001G>A (p.R334Q) alteration is located in exon 10 (coding exon 8) of the MSL1 gene. This alteration results from a G to A substitution at nucleotide position 1001, causing the arginine (R) at amino acid position 334 to be replaced by a glutamine (Q). 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

Uncertain

0.51

BayesDel_addAF

Uncertain

0.096

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.074

T;T;.

Eigen

Uncertain

0.54

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.97

D;D;D

M_CAP

Benign

0.017

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-0.65

MutationAssessor

Benign

0.69

N;.;.

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.4

N;.;.

REVEL

Uncertain

0.33

Sift

Uncertain

0.0050

D;.;.

Sift4G

Uncertain

0.018

D;D;D

Vest4

0.47

MutPred

0.29

Loss of MoRF binding (P = 0.039);.;.;

MVP

0.44

MPC

1.6

ClinPred

0.79

GERP RS

6.0

Varity_R

0.29

gMVP

0.76

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