Variant rs530217423 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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:2

Conservation

PhyloP100: -0.146

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=0.0034320652).

BP6

Variant 4-4859985-C-T is Benign according to our data. Variant chr4-4859985-C-T is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSX1	NM_002448.3 linkuse as main transcript	c.86C>T	p.Ala29Val	missense_variant	1/2	ENST00000382723.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSX1	ENST00000382723.5 linkuse as main transcript	c.86C>T	p.Ala29Val	missense_variant	1/2	1	NM_002448.3	P1

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

GnomAD3 exomes

AF:

0.0118

AC:

1021

AN:

86270

Hom.:

AF XY:

0.00818

AC XY:

393

AN XY:

48048

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 SAS 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

Gnomad4 AFR exome

AF:

0.000341

Gnomad4 AMR exome

AF:

0.0558

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:

0.0000181

Gnomad4 OTH exome

AF:

0.00137

GnomAD4 genome

AF:

0.00331

AC:

504

AN:

152122

Hom.:

Cov.:

AF XY:

0.00368

AC XY:

274

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.000626

Gnomad4 AMR

AF:

0.0302

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00167

Hom.:

Bravo

AF:

0.00563

ExAC

AF:

0.00140

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hypoplastic enamel-onycholysis-hypohidrosis syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 18, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.31

Cadd

Benign

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

MutationTaster

Benign

1.0

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

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.033

gMVP

0.41

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