rs79213434

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004527.4(MEOX1):c.11C>T(p.Ala4Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,564,174 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A4A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0076 ( 15 hom., cov: 32)

Exomes 𝑓: 0.00072 ( 14 hom. )

Consequence

MEOX1
NM_004527.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.620

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

Klippel-Feil syndrome 2, autosomal recessive
Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
isolated Klippel-Feil syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

MEOX1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019446313).

BP6

Variant 17-43661524-G-A is Benign according to our data. Variant chr17-43661524-G-A is described in ClinVar as Benign. ClinVar VariationId is 259423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0076 (1157/152176) while in subpopulation AFR AF = 0.0266 (1106/41518). AF 95% confidence interval is 0.0253. There are 15 homozygotes in GnomAd4. There are 547 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 15 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEOX1	NM_004527.4 link	c.11C>T	p.Ala4Val	missense_variant	Exon 1 of 3	ENST00000318579.9	NP_004518.1	P50221-1
MEOX1	NM_013999.4 link	c.11C>T	p.Ala4Val	missense_variant	Exon 1 of 2		NP_054705.1	P50221-2
MEOX1	XM_011524818.3 link	c.11C>T	p.Ala4Val	missense_variant	Exon 1 of 3		XP_011523120.1
MEOX1	NM_001040002.2 link	c.-204-131C>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.11C>T	p.Ala4Val	missense_variant	Exon 1 of 3	1	NM_004527.4	ENSP00000321684.4	P50221-1
MEOX1	ENST00000549132.2 link	c.11C>T	p.Ala4Val	missense_variant	Exon 1 of 2	1		ENSP00000449049.2	P50221-2
MEOX1	ENST00000393661.2 link	c.-204-131C>T		intron_variant	Intron 1 of 3	3		ENSP00000377271.2	P50221-3

Frequencies

GnomAD3 genomes

AF:

0.00758

AC:

1152

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00383

GnomAD2 exomes

AF:

0.00191

AC:

372

AN:

194438

AF XY:

0.00151

show subpopulations

Gnomad AFR exome

AF:

0.0266

Gnomad AMR exome

AF:

0.000982

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000670

Gnomad FIN exome

AF:

0.000339

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.000645

GnomAD4 exome

AF:

0.000719

AC:

1015

AN:

1411998

Hom.:

Cov.:

AF XY:

0.000611

AC XY:

426

AN XY:

697580

show subpopulations

African (AFR)

AF:

0.0264

AC:

843

AN:

31950

American (AMR)

AF:

0.00116

AC:

AN:

36100

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24186

East Asian (EAS)

AF:

0.0000260

AC:

AN:

38492

South Asian (SAS)

AF:

0.0000870

AC:

AN:

80438

European-Finnish (FIN)

AF:

0.000275

AC:

AN:

50946

Middle Eastern (MID)

AF:

0.000245

AC:

AN:

4086

European-Non Finnish (NFE)

AF:

0.0000184

AC:

AN:

1087768

Other (OTH)

AF:

0.00150

AC:

AN:

58032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

134

179

224

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00760

AC:

1157

AN:

152176

Hom.:

Cov.:

AF XY:

0.00735

AC XY:

547

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0266

AC:

1106

AN:

41518

American (AMR)

AF:

0.00242

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67984

Other (OTH)

AF:

0.00379

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

115

173

230

288

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00361

Hom.:

Bravo

AF:

0.00834

ESP6500AA

AF:

0.0211

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00203

AC:

244

Asia WGS

AF:

0.00115

AC:

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

0.069

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.44

CADD

Benign

7.0

(source)

DANN

Benign

0.51

DEOGEN2

Benign

0.029

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.084

LIST_S2

Benign

0.69

T;T

MetaRNN

Benign

0.0019

T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

-0.36

N;N

PhyloP100

0.62

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.82

N;N

REVEL

Benign

0.16

Sift

Benign

0.68

T;T

Sift4G

Benign

0.67

T;T

Polyphen

0.0010

B;.

Vest4

0.031

MVP

0.77

MPC

0.10

ClinPred

0.0061

GERP RS

-1.8

PromoterAI

0.031

Neutral

(source)

Varity_R

0.034

gMVP

0.22

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over