rs530217423

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002448.3(MSX1):c.86C>T(p.Ala29Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00136 in 1,483,012 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A29S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0033 ( 16 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 77 hom. )

Consequence

MSX1
NM_002448.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.146

Publications

0 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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034320652).

BP6

Variant 4-4859985-C-T is Benign according to our data. Variant chr4-4859985-C-T is described in ClinVar as Benign. ClinVar VariationId is 461604.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0533 is higher than 0.05.

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.86C>T	p.Ala29Val	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.86C>T	p.Ala29Val	missense	Exon 1 of 2	ENSP00000372170.4	P28360
ENSG00000308455	ENST00000834195.1		n.304-3196G>A		intron	N/A
ENSG00000308455	ENST00000834196.1		n.49-3196G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00330

AC:

502

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000628

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0301

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:

0.000147

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.0118

AC:

1021

AN:

86270

AF XY:

0.00818

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0704

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:

0.00625

GnomAD4 exome

AF:

0.00114

AC:

1519

AN:

1330890

Hom.:

Cov.:

AF XY:

0.000963

AC XY:

631

AN XY:

655548

show subpopulations

African (AFR)

AF:

0.000341

AC:

AN:

26410

American (AMR)

AF:

0.0558

AC:

1416

AN:

25394

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22496

East Asian (EAS)

AF:

0.00

AC:

AN:

30212

South Asian (SAS)

AF:

0.00

AC:

AN:

70268

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46744

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4168

European-Non Finnish (NFE)

AF:

0.0000181

AC:

AN:

1050530

Other (OTH)

AF:

0.00137

AC:

AN:

54668

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.584

Heterozygous variant carriers

110

165

220

275

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00331

AC:

504

AN:

152122

Hom.:

Cov.:

AF XY:

0.00368

AC XY:

274

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.000626

AC:

AN:

41546

American (AMR)

AF:

0.0302

AC:

461

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

67948

Other (OTH)

AF:

0.00332

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

122

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00167

Hom.:

Bravo

AF:

0.00563

ExAC

AF:

0.00140

AC:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Hypoplastic enamel-onycholysis-hypohidrosis syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.66

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.45

MetaRNN

Benign

0.0034

MetaSVM

Benign

-0.39

MutationAssessor

Benign

0.41

PhyloP100

-0.15

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.36

REVEL

Benign

0.23

Sift

Benign

0.41

Sift4G

Benign

0.34

Vest4

0.18

MPC

0.70

ClinPred

0.015

GERP RS

0.15

PromoterAI

-0.053

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.033

gMVP

0.41

Mutation Taster

=100/0

polymorphism (auto)

(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