Variant chr4-4859988-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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 (★).

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

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 -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 id 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/exons	MANE	Protein	UniProt
MSX1	NM_002448.3 linkuse as main transcript	c.89G>A	p.Gly30Asp	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 linkuse as main transcript	c.89G>A	p.Gly30Asp	missense_variant	1/2	1	NM_002448.3	ENSP00000372170.4		P28360

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000106

AC:

AN:

94474

Hom.:

AF XY:

0.0000191

AC XY:

AN XY:

52378

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 SAS 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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000759

Gnomad4 OTH exome

AF:

0.00

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

Likely benign, criteria provided, single submitter

clinical testing

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Apr 02, 2020

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

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

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

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.089

gMVP

0.46

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