4-4860018-C-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002448.3(MSX1):c.119C>G(p.Ala40Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 1,500,962 control chromosomes in the GnomAD database, including 18,800 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1594 hom., cov: 33)

Exomes 𝑓: 0.16 ( 17206 hom. )

Consequence

MSX1
NM_002448.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.761

Variant links:

Genes affected

MSX1 (HGNC:7391): (msh homeobox 1) This gene encodes a member of the muscle segment homeobox gene family. The encoded protein functions as a transcriptional repressor during embryogenesis through interactions with components of the core transcription complex and other homeoproteins. It may also have roles in limb-pattern formation, craniofacial development, particularly odontogenesis, and tumor growth inhibition. Mutations in this gene, which was once known as homeobox 7, have been associated with nonsyndromic cleft lip with or without cleft palate 5, Witkop syndrome, Wolf-Hirschom syndrome, and autosomoal dominant hypodontia. [provided by RefSeq, Jul 2008]

MSX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014262795).

BP6

Variant 4-4860018-C-G is Benign according to our data. Variant chr4-4860018-C-G is described in ClinVar as [Benign]. Clinvar id is 802050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-4860018-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSX1	NM_002448.3 link	c.119C>G	p.Ala40Gly	missense_variant	Exon 1 of 2	ENST00000382723.5	NP_002439.2	P28360

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSX1	ENST00000382723.5 link	c.119C>G	p.Ala40Gly	missense_variant	Exon 1 of 2	1	NM_002448.3	ENSP00000372170.4		P28360

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

21331

AN:

151922

Hom.:

1595

Cov.:

show subpopulations

Gnomad AFR

AF:

0.103

Gnomad AMI

AF:

0.0899

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.196

Gnomad EAS

AF:

0.0521

Gnomad SAS

AF:

0.117

Gnomad FIN

AF:

0.211

Gnomad MID

AF:

0.210

Gnomad NFE

AF:

0.164

Gnomad OTH

AF:

0.129

GnomAD3 exomes

AF:

0.150

AC:

15047

AN:

100178

Hom.:

1241

AF XY:

0.149

AC XY:

8314

AN XY:

55658

show subpopulations

Gnomad AFR exome

AF:

0.113

Gnomad AMR exome

AF:

0.0965

Gnomad ASJ exome

AF:

0.198

Gnomad EAS exome

AF:

0.0517

Gnomad SAS exome

AF:

0.125

Gnomad FIN exome

AF:

0.208

Gnomad NFE exome

AF:

0.173

Gnomad OTH exome

AF:

0.164

GnomAD4 exome

AF:

0.156

AC:

210803

AN:

1348932

Hom.:

17206

Cov.:

AF XY:

0.155

AC XY:

103375

AN XY:

665042

show subpopulations

Gnomad4 AFR exome

AF:

0.103

Gnomad4 AMR exome

AF:

0.100

Gnomad4 ASJ exome

AF:

0.189

Gnomad4 EAS exome

AF:

0.0618

Gnomad4 SAS exome

AF:

0.119

Gnomad4 FIN exome

AF:

0.209

Gnomad4 NFE exome

AF:

0.162

Gnomad4 OTH exome

AF:

0.147

GnomAD4 genome

AF:

0.140

AC:

21327

AN:

152030

Hom.:

1594

Cov.:

AF XY:

0.141

AC XY:

10501

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.103

Gnomad4 AMR

AF:

0.118

Gnomad4 ASJ

AF:

0.196

Gnomad4 EAS

AF:

0.0521

Gnomad4 SAS

AF:

0.116

Gnomad4 FIN

AF:

0.211

Gnomad4 NFE

AF:

0.164

Gnomad4 OTH

AF:

0.128

Alfa

AF:

0.159

Hom.:

447

Bravo

AF:

0.131

ESP6500AA

AF:

0.0963

AC:

241

ESP6500EA

AF:

0.141

AC:

677

ExAC

AF:

0.106

AC:

2136

Asia WGS

AF:

0.0850

AC:

291

AN:

3420

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hypoplastic enamel-onycholysis-hypohidrosis syndrome

Benign:2

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 28965043, 28204848, 16723652, 15379328, 21866112, 25565750, 21740177) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.25

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.69

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.72

MetaRNN

Benign

0.0014

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.3

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.30

REVEL

Benign

0.15

Sift

Benign

0.26

Sift4G

Benign

0.32

Vest4

0.061

MPC

0.72

ClinPred

0.0035

GERP RS

2.9

Varity_R

0.058

gMVP

0.39

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