Variant 17-40129280-C-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.1028C>T(p.Pro343Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000634 in 1,420,198 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: not found (cov: 31)

Exomes 𝑓: 0.0000063 ( 0 hom. )

Consequence

MSL1
NM_001365919.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.21

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:

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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=0.229929).

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.1028C>T	p.Pro343Leu	missense_variant	3/9	ENST00000398532.9	NP_001352848.1
MSL1	NM_001365920.1 linkuse as main transcript	c.1028C>T	p.Pro343Leu	missense_variant	3/8		NP_001352849.1
MSL1	NM_001365921.2 linkuse as main transcript	c.1028C>T	p.Pro343Leu	missense_variant	3/3		NP_001352850.1
MSL1	NM_001012241.2 linkuse as main transcript	c.239C>T	p.Pro80Leu	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.1028C>T	p.Pro343Leu	missense_variant	3/9	1	NM_001365919.1	ENSP00000381543.3		Q68DK7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000330

AC:

AN:

211856

Hom.:

AF XY:

0.0000345

AC XY:

AN XY:

115994

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000300

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000634

AC:

AN:

1420198

Hom.:

Cov.:

AF XY:

0.00000709

AC XY:

AN XY:

705674

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000281

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.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.00000828

AC:

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

Jun 16, 2023

The c.239C>T (p.P80L) alteration is located in exon 4 (coding exon 2) of the MSL1 gene. This alteration results from a C to T substitution at nucleotide position 239, causing the proline (P) at amino acid position 80 to be replaced by a leucine (L). 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

0.14

BayesDel_addAF

Uncertain

0.020

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Benign

0.95

DEOGEN2

Benign

0.070

T;T;T;.

Eigen

Uncertain

0.62

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D;D;D

M_CAP

Benign

0.0048

MetaRNN

Benign

0.23

T;T;T;T

MetaSVM

Benign

-0.53

MutationAssessor

Benign

1.4

L;.;.;.

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.6

N;.;.;.

REVEL

Benign

0.27

Sift

Uncertain

0.0020

D;.;.;.

Sift4G

Uncertain

0.0080

D;D;D;T

Polyphen

1.0

D;.;.;.

Vest4

0.46

MutPred

0.37

Gain of helix (P = 0.0022);Gain of helix (P = 0.0022);Gain of helix (P = 0.0022);.;

MVP

0.30

MPC

1.6

ClinPred

0.26

GERP RS

6.0

Varity_R

0.059

gMVP

0.34

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