NM_002448.3:c.38G>C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_002448.3(MSX1):c.38G>C(p.Gly13Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000735 in 1,496,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G13V) has been classified as Uncertain significance.

Frequency

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

Exomes 𝑓: 0.0000074 ( 0 hom. )

Consequence

MSX1
NM_002448.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.75

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

orofacial cleft 5
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
tooth agenesis, selective, 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
tooth agenesis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
tooth and nail syndrome
Inheritance: AD Classification: SUPPORTIVE, LIMITED, NO_KNOWN Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

MSX1 links:

ENSG00000308455 (HGNC:):

ENSG00000308455 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.4122062).

BS2

High AC in GnomAdExome4 at 10 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002448.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSX1	NM_002448.3	MANE Select	c.38G>C	p.Gly13Ala	missense	Exon 1 of 2	NP_002439.2	P28360

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MSX1	ENST00000382723.5	TSL:1 MANE Select	c.38G>C	p.Gly13Ala	missense	Exon 1 of 2	ENSP00000372170.4	P28360
ENSG00000308455	ENST00000834195.1		n.304-3148C>G		intron	N/A
ENSG00000308455	ENST00000834196.1		n.49-3148C>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151988

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

GnomAD2 exomes

AF:

0.00000987

AC:

AN:

101290

AF XY:

0.0000177

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000744

AC:

AN:

1344822

Hom.:

Cov.:

AF XY:

0.0000106

AC XY:

AN XY:

663452

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27146

American (AMR)

AF:

0.00

AC:

AN:

28724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23376

East Asian (EAS)

AF:

0.00

AC:

AN:

30078

South Asian (SAS)

AF:

0.0000411

AC:

AN:

73050

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47320

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3986

European-Non Finnish (NFE)

AF:

0.00000663

AC:

AN:

1055914

Other (OTH)

AF:

0.00

AC:

AN:

55228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151988

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41422

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10554

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67936

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Uncertain

0.067

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

Eigen

Benign

-0.13

Eigen_PC

Benign

0.042

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.81

M_CAP

Pathogenic

0.97

MetaRNN

Benign

0.41

MetaSVM

Uncertain

0.33

MutationAssessor

Benign

1.7

PhyloP100

1.8

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-1.1

REVEL

Benign

0.28

Sift

Uncertain

0.011

Sift4G

Benign

0.24

Vest4

0.11

MVP

0.94

MPC

1.8

ClinPred

0.86

GERP RS

4.6

PromoterAI

-0.11

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.24

gMVP

0.63

Mutation Taster

=88/12

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over