NM_004527.4:c.80C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004527.4(MEOX1):c.80C>T(p.Ser27Leu) variant causes a missense change. The variant allele was found at a frequency of 0.11 in 1,610,480 control chromosomes in the GnomAD database, including 12,211 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.16 ( 2822 hom., cov: 31)

Exomes 𝑓: 0.10 ( 9389 hom. )

Consequence

MEOX1
NM_004527.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 4.08

Variant links:

Genes affected

MEOX1 (HGNC:7013): (mesenchyme homeobox 1) This gene encodes a member of a subfamily of non-clustered, diverged, antennapedia-like homeobox-containing genes. The encoded protein may play a role in the molecular signaling network regulating somite development. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

MEOX1 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=0.0013354421).

BP6

Variant 17-43661455-G-A is Benign according to our data. Variant chr17-43661455-G-A is described in ClinVar as [Benign]. Clinvar id is 259424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-43661455-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEOX1	NM_004527.4 link	c.80C>T	p.Ser27Leu	missense_variant	Exon 1 of 3	ENST00000318579.9	NP_004518.1	P50221-1
MEOX1	NM_013999.4 link	c.80C>T	p.Ser27Leu	missense_variant	Exon 1 of 2		NP_054705.1	P50221-2
MEOX1	XM_011524818.3 link	c.80C>T	p.Ser27Leu	missense_variant	Exon 1 of 3		XP_011523120.1
MEOX1	NM_001040002.2 link	c.-204-62C>T		intron_variant	Intron 1 of 3		NP_001035091.1	P50221-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MEOX1	ENST00000318579.9 link	c.80C>T	p.Ser27Leu	missense_variant	Exon 1 of 3	1	NM_004527.4	ENSP00000321684.4	P50221-1
MEOX1	ENST00000549132.2 link	c.80C>T	p.Ser27Leu	missense_variant	Exon 1 of 2	1		ENSP00000449049.2	P50221-2
MEOX1	ENST00000393661.2 link	c.-204-62C>T		intron_variant	Intron 1 of 3	3		ENSP00000377271.2	P50221-3

Frequencies

GnomAD3 genomes

AF:

0.160

AC:

24339

AN:

151798

Hom.:

2817

Cov.:

show subpopulations

Gnomad AFR

AF:

0.323

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.0755

Gnomad ASJ

AF:

0.0995

Gnomad EAS

AF:

0.00155

Gnomad SAS

AF:

0.0706

Gnomad FIN

AF:

0.137

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.109

Gnomad OTH

AF:

0.127

GnomAD3 exomes

AF:

0.103

AC:

24847

AN:

242056

Hom.:

1884

AF XY:

0.101

AC XY:

13315

AN XY:

131940

show subpopulations

Gnomad AFR exome

AF:

0.334

Gnomad AMR exome

AF:

0.0505

Gnomad ASJ exome

AF:

0.0974

Gnomad EAS exome

AF:

0.000277

Gnomad SAS exome

AF:

0.0828

Gnomad FIN exome

AF:

0.129

Gnomad NFE exome

AF:

0.106

Gnomad OTH exome

AF:

0.0950

GnomAD4 exome

AF:

0.104

AC:

152340

AN:

1458564

Hom.:

9389

Cov.:

AF XY:

0.104

AC XY:

75212

AN XY:

725354

show subpopulations

Gnomad4 AFR exome

AF:

0.327

Gnomad4 AMR exome

AF:

0.0536

Gnomad4 ASJ exome

AF:

0.0980

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0858

Gnomad4 FIN exome

AF:

0.125

Gnomad4 NFE exome

AF:

0.104

Gnomad4 OTH exome

AF:

0.105

GnomAD4 genome

AF:

0.160

AC:

24364

AN:

151916

Hom.:

2822

Cov.:

AF XY:

0.158

AC XY:

11701

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.322

Gnomad4 AMR

AF:

0.0753

Gnomad4 ASJ

AF:

0.0995

Gnomad4 EAS

AF:

0.00155

Gnomad4 SAS

AF:

0.0710

Gnomad4 FIN

AF:

0.137

Gnomad4 NFE

AF:

0.109

Gnomad4 OTH

AF:

0.126

Alfa

AF:

0.115

Hom.:

2113

Bravo

AF:

0.161

TwinsUK

AF:

0.108

AC:

402

ALSPAC

AF:

0.102

AC:

394

ESP6500AA

AF:

0.302

AC:

1313

ESP6500EA

AF:

0.101

AC:

857

ExAC

AF:

0.109

AC:

13196

Asia WGS

AF:

0.0420

AC:

147

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;.

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.75

T;T

MetaRNN

Benign

0.0013

T;T

MetaSVM

Benign

-1.3

MutationAssessor

Uncertain

2.2

M;M

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.9

N;D

REVEL

Uncertain

0.33

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.011

D;D

Polyphen

0.71

P;.

Vest4

0.059

MPC

0.090

ClinPred

0.090

GERP RS

4.7

Varity_R

0.31

gMVP

0.39

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