Variant 4-4859976-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_002448.3(MSX1):c.77G>C(p.Gly26Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000194 in 1,488,566 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

MSX1
NM_002448.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.28

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.034795195).

BP6

Variant 4-4859976-G-C is Benign according to our data. Variant chr4-4859976-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1563606.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-4859976-G-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00019 (254/1336448) while in subpopulation MID AF= 0.0019 (8/4210). AF 95% confidence interval is 0.000945. There are 0 homozygotes in gnomad4_exome. There are 123 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd4 at 35 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSX1	NM_002448.3 link	c.77G>C	p.Gly26Ala	missense_variant	1/2	ENST00000382723.5	NP_002439.2	P28360

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSX1	ENST00000382723.5 link	c.77G>C	p.Gly26Ala	missense_variant	1/2	1	NM_002448.3	ENSP00000372170.4		P28360

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000300

AC:

AN:

89896

Hom.:

AF XY:

0.000300

AC XY:

AN XY:

49932

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000129

Gnomad ASJ exome

AF:

0.00247

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000672

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000258

Gnomad OTH exome

AF:

0.000399

GnomAD4 exome

AF:

0.000190

AC:

254

AN:

1336448

Hom.:

Cov.:

AF XY:

0.000187

AC XY:

123

AN XY:

658434

show subpopulations

Gnomad4 AFR exome

AF:

0.0000750

Gnomad4 AMR exome

AF:

0.000110

Gnomad4 ASJ exome

AF:

0.00249

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000842

Gnomad4 FIN exome

AF:

0.0000213

Gnomad4 NFE exome

AF:

0.000155

Gnomad4 OTH exome

AF:

0.000255

GnomAD4 genome

AF:

0.000230

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000641

Hom.:

Bravo

AF:

0.000253

ExAC

AF:

0.000142

AC:

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

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.27

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.47

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.69

M_CAP

Pathogenic

0.97

MetaRNN

Benign

0.035

MetaSVM

Benign

-0.48

MutationAssessor

Benign

1.2

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.48

REVEL

Benign

0.29

Sift

Benign

0.41

Sift4G

Benign

0.72

Vest4

0.27

MVP

0.96

MPC

0.76

ClinPred

0.018

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.068

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