rs1414674827

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4BP6_ModerateBS2

The NM_002448.3(MSX1):c.89G>A(p.Gly30Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000597 in 1,340,592 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G30A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000060 ( 0 hom. )

Consequence

MSX1
NM_002448.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.92

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 Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

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 -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.39773577).

BP6

Variant 4-4859988-G-A is Benign according to our data. Variant chr4-4859988-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 931187.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSX1	NM_002448.3 link	c.89G>A	p.Gly30Asp	missense_variant	Exon 1 of 2	ENST00000382723.5	NP_002439.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
MSX1	ENST00000382723.5 link	c.89G>A	p.Gly30Asp	missense_variant	Exon 1 of 2	1	NM_002448.3	ENSP00000372170.4
ENSG00000308455	ENST00000834195.1 link	n.304-3199C>T		intron_variant	Intron 2 of 2
ENSG00000308455	ENST00000834196.1 link	n.49-3199C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000106

AC:

AN:

94474

AF XY:

0.0000191

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:

0.0000309

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000597

AC:

AN:

1340592

Hom.:

Cov.:

AF XY:

0.00000908

AC XY:

AN XY:

660530

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26808

American (AMR)

AF:

0.00

AC:

AN:

27932

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23030

East Asian (EAS)

AF:

0.00

AC:

AN:

30428

South Asian (SAS)

AF:

0.00

AC:

AN:

72088

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46980

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4240

European-Non Finnish (NFE)

AF:

0.00000759

AC:

AN:

1053928

Other (OTH)

AF:

0.00

AC:

AN:

55158

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.419

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

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hypoplastic enamel-onycholysis-hypohidrosis syndrome

Benign:1

Apr 02, 2020

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was classified as: Likely benign. The following ACMG criteria were applied in classifying this variant: BP4,BS2. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.31

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.35

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.66

M_CAP

Pathogenic

0.93

MetaRNN

Benign

0.40

MetaSVM

Uncertain

-0.14

MutationAssessor

Benign

1.7

PhyloP100

1.9

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.45

REVEL

Uncertain

0.41

Sift

Benign

0.15

Sift4G

Uncertain

0.023

Vest4

0.34

MVP

0.87

MPC

1.1

ClinPred

0.27

GERP RS

2.7

PromoterAI

-0.0060

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.089

gMVP

0.46

Mutation Taster

=90/10

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over