Variant chr17-40134279-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001365919.1(MSL1):c.1755G>T(p.Gln585His) variant causes a missense, splice region 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. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MSL1
NM_001365919.1 missense, splice_region

Scores

Splicing: ADA: 0.8113

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.13

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 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=0.19000703).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSL1	NM_001365919.1 linkuse as main transcript	c.1755G>T	p.Gln585His	missense_variant, splice_region_variant	9/9	ENST00000398532.9	NP_001352848.1
MSL1	NM_001365920.1 linkuse as main transcript	c.1707G>T	p.Gln569His	missense_variant, splice_region_variant	8/8		NP_001352849.1
MSL1	NM_001012241.2 linkuse as main transcript	c.966G>T	p.Gln322His	missense_variant, splice_region_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.1755G>T	p.Gln585His	missense_variant, splice_region_variant	9/9	1	NM_001365919.1	ENSP00000381543.3		Q68DK7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1400700

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

691192

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Aug 05, 2024

The c.966G>T (p.Q322H) alteration is located in exon 10 (coding exon 8) of the MSL1 gene. This alteration results from a G to T substitution at nucleotide position 966, causing the glutamine (Q) at amino acid position 322 to be replaced by a histidine (H). 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

Pathogenic

0.65

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

DANN

Benign

0.90

DEOGEN2

Benign

0.099

T;T;.

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.049

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;.;.

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.6

N;.;.

REVEL

Benign

0.094

Sift

Uncertain

0.0060

D;.;.

Sift4G

Uncertain

0.0070

D;D;D

Vest4

0.28

MutPred

0.20

Loss of solvent accessibility (P = 0.0238);.;.;

MVP

0.26

MPC

1.5

ClinPred

0.61

GERP RS

2.9

Varity_R

0.16

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.81

dbscSNV1_RF

Benign

0.53

SpliceAI score (max)

0.17

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