Genetic Variant MNX1:p.Ala132_Ala134dup (chr7-157009949-A-AGCGGCGGCG) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBA1

The NM_005515.4(MNX1):c.393_401dupCGCCGCCGC(p.Ala132_Ala134dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A134A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.11 ( 1095 hom., cov: 0)

Exomes 𝑓: 0.073 ( 2158 hom. )

Failed GnomAD Quality Control

Consequence

MNX1
NM_005515.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 1.54

Publications

4 publications found

Variant links:

Genes affected

MNX1 (HGNC:4979): (motor neuron and pancreas homeobox 1) This gene encodes a nuclear protein, which contains a homeobox domain and is a transcription factor. Mutations in this gene result in Currarino syndrome, an autosomic dominant congenital malformation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

MNX1 links:

MNX1-AS1 (HGNC:48954): (MNX1 antisense RNA 1 (head to head))

MNX1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_005515.4

BP6

Variant 7-157009949-A-AGCGGCGGCG is Benign according to our data. Variant chr7-157009949-A-AGCGGCGGCG is described in ClinVar as [Benign]. Clinvar id is 1170017.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MNX1	NM_005515.4 link	c.393_401dupCGCCGCCGC	p.Ala132_Ala134dup	disruptive_inframe_insertion	Exon 1 of 3	ENST00000252971.11	NP_005506.3	P50219-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MNX1	ENST00000252971.11 link	c.393_401dupCGCCGCCGC	p.Ala132_Ala134dup	disruptive_inframe_insertion	Exon 1 of 3	1	NM_005515.4	ENSP00000252971.5	P50219-1
MNX1-AS1	ENST00000818900.1 link	n.296+1925_296+1933dupGGCGGCGGC		intron_variant	Intron 1 of 1
MNX1-AS1	ENST00000818901.1 link	n.50+840_50+848dupGGCGGCGGC		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

13620

AN:

129580

Hom.:

1092

Cov.:

show subpopulations

Gnomad AFR

AF:

0.188

Gnomad AMI

AF:

0.0701

Gnomad AMR

AF:

0.0872

Gnomad ASJ

AF:

0.0352

Gnomad EAS

AF:

0.159

Gnomad SAS

AF:

0.121

Gnomad FIN

AF:

0.0717

Gnomad MID

AF:

0.0244

Gnomad NFE

AF:

0.0654

Gnomad OTH

AF:

0.0729

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0734

AC:

56928

AN:

775888

Hom.:

2158

Cov.:

AF XY:

0.0734

AC XY:

26605

AN XY:

362474

show subpopulations

African (AFR)

AF:

0.200

AC:

2956

AN:

14752

American (AMR)

AF:

0.0663

AC:

AN:

1342

Ashkenazi Jewish (ASJ)

AF:

0.0344

AC:

171

AN:

4972

East Asian (EAS)

AF:

0.125

AC:

535

AN:

4292

South Asian (SAS)

AF:

0.120

AC:

1932

AN:

16092

European-Finnish (FIN)

AF:

0.0164

AC:

AN:

1338

Middle Eastern (MID)

AF:

0.0455

AC:

AN:

1582

European-Non Finnish (NFE)

AF:

0.0695

AC:

49052

AN:

705676

Other (OTH)

AF:

0.0812

AC:

2099

AN:

25842

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

2012

4024

6035

8047

10059

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2594

5188

7782

10376

12970

<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:

0.105

AC:

13623

AN:

129588

Hom.:

1095

Cov.:

AF XY:

0.107

AC XY:

6698

AN XY:

62824

show subpopulations

African (AFR)

AF:

0.188

AC:

6596

AN:

35016

American (AMR)

AF:

0.0869

AC:

1172

AN:

13482

Ashkenazi Jewish (ASJ)

AF:

0.0352

AC:

113

AN:

3214

East Asian (EAS)

AF:

0.160

AC:

660

AN:

4132

South Asian (SAS)

AF:

0.121

AC:

458

AN:

3800

European-Finnish (FIN)

AF:

0.0717

AC:

479

AN:

6684

Middle Eastern (MID)

AF:

0.0263

AC:

AN:

228

European-Non Finnish (NFE)

AF:

0.0654

AC:

3954

AN:

60456

Other (OTH)

AF:

0.0725

AC:

131

AN:

1806

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

510

1020

1530

2040

2550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

288

432

576

720

<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:

0.0478

Hom.:

1464

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Oct 20, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.5

Mutation Taster

=69/31

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

7-157009949-AGCGGCGGCGGCGGCGGCG-AGCGGCGGCGGCGGCGGCGGCGGCGGCG

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