Variant 4-4860247-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002448.3(MSX1):c.348C>T(p.Gly116=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0584 in 1,586,738 control chromosomes in the GnomAD database, including 3,702 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 358 hom., cov: 32)

Exomes 𝑓: 0.058 ( 3344 hom. )

Consequence

MSX1
NM_002448.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.484

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 4-4860247-C-T is Benign according to our data. Variant chr4-4860247-C-T is described in ClinVar as [Benign]. Clinvar id is 1165584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-4860247-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.484 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.157 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.348C>T	p.Gly116=	synonymous_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.348C>T	p.Gly116=	synonymous_variant	1/2	1	NM_002448.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0634

AC:

9638

AN:

152040

Hom.:

358

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0832

Gnomad AMI

AF:

0.148

Gnomad AMR

AF:

0.0594

Gnomad ASJ

AF:

0.0343

Gnomad EAS

AF:

0.0779

Gnomad SAS

AF:

0.167

Gnomad FIN

AF:

0.0437

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0471

Gnomad OTH

AF:

0.0727

GnomAD3 exomes

AF:

0.0678

AC:

14096

AN:

208056

Hom.:

701

AF XY:

0.0725

AC XY:

8438

AN XY:

116370

show subpopulations

Gnomad AFR exome

AF:

0.0838

Gnomad AMR exome

AF:

0.0436

Gnomad ASJ exome

AF:

0.0401

Gnomad EAS exome

AF:

0.0691

Gnomad SAS exome

AF:

0.174

Gnomad FIN exome

AF:

0.0445

Gnomad NFE exome

AF:

0.0477

Gnomad OTH exome

AF:

0.0628

GnomAD4 exome

AF:

0.0578

AC:

82954

AN:

1434586

Hom.:

3344

Cov.:

AF XY:

0.0610

AC XY:

43529

AN XY:

713272

show subpopulations

Gnomad4 AFR exome

AF:

0.0857

Gnomad4 AMR exome

AF:

0.0449

Gnomad4 ASJ exome

AF:

0.0392

Gnomad4 EAS exome

AF:

0.102

Gnomad4 SAS exome

AF:

0.170

Gnomad4 FIN exome

AF:

0.0438

Gnomad4 NFE exome

AF:

0.0480

Gnomad4 OTH exome

AF:

0.0647

GnomAD4 genome

AF:

0.0634

AC:

9642

AN:

152152

Hom.:

358

Cov.:

AF XY:

0.0653

AC XY:

4860

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.0831

Gnomad4 AMR

AF:

0.0593

Gnomad4 ASJ

AF:

0.0343

Gnomad4 EAS

AF:

0.0782

Gnomad4 SAS

AF:

0.166

Gnomad4 FIN

AF:

0.0437

Gnomad4 NFE

AF:

0.0471

Gnomad4 OTH

AF:

0.0720

Alfa

AF:

0.0528

Hom.:

Bravo

AF:

0.0635

Asia WGS

AF:

0.157

AC:

545

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	May 05, 2021	This variant is associated with the following publications: (PMID: 25565750, 23731659) -

Hypoplastic enamel-onycholysis-hypohidrosis syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 20, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.98

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