Variant rs12532 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.*276A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 457,632 control chromosomes in the GnomAD database, including 28,816 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10750 hom., cov: 28)

Exomes 𝑓: 0.33 ( 18066 hom. )

Consequence

MSX1
NM_002448.3 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.07

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 (BayesDel_noAF=-0.84).

BP6

Variant 4-4863419-A-G is Benign according to our data. Variant chr4-4863419-A-G is described in ClinVar as [Benign]. Clinvar id is 530788.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSX1	NM_002448.3 link	c.*276A>G		3_prime_UTR_variant	2/2	ENST00000382723.5	NP_002439.2	P28360

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSX1	ENST00000382723.5 link	c.*276A>G		3_prime_UTR_variant	2/2	1	NM_002448.3	ENSP00000372170.4		P28360

Frequencies

GnomAD3 genomes

AF:

0.363

AC:

54985

AN:

151446

Hom.:

10724

Cov.:

show subpopulations

Gnomad AFR

AF:

0.439

Gnomad AMI

AF:

0.230

Gnomad AMR

AF:

0.460

Gnomad ASJ

AF:

0.217

Gnomad EAS

AF:

0.608

Gnomad SAS

AF:

0.289

Gnomad FIN

AF:

0.379

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.290

Gnomad OTH

AF:

0.343

GnomAD4 exome

AF:

0.329

AC:

100810

AN:

306068

Hom.:

18066

Cov.:

AF XY:

0.325

AC XY:

52071

AN XY:

160186

show subpopulations

Gnomad4 AFR exome

AF:

0.447

Gnomad4 AMR exome

AF:

0.495

Gnomad4 ASJ exome

AF:

0.222

Gnomad4 EAS exome

AF:

0.602

Gnomad4 SAS exome

AF:

0.275

Gnomad4 FIN exome

AF:

0.387

Gnomad4 NFE exome

AF:

0.293

Gnomad4 OTH exome

AF:

0.328

GnomAD4 genome

AF:

0.363

AC:

55071

AN:

151564

Hom.:

10750

Cov.:

AF XY:

0.370

AC XY:

27397

AN XY:

74032

show subpopulations

Gnomad4 AFR

AF:

0.439

Gnomad4 AMR

AF:

0.461

Gnomad4 ASJ

AF:

0.217

Gnomad4 EAS

AF:

0.607

Gnomad4 SAS

AF:

0.289

Gnomad4 FIN

AF:

0.379

Gnomad4 NFE

AF:

0.290

Gnomad4 OTH

AF:

0.349

Alfa

AF:

0.306

Hom.:

4233

Bravo

AF:

0.373

Asia WGS

AF:

0.436

AC:

1515

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	This variant is associated with the following publications: (PMID: 23549991, 23231047, 24603642) -

Hypoplastic enamel-onycholysis-hypohidrosis syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 06, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.9

DANN

Benign

0.78

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