chr7-157009949-A-AGCGGCGGCG

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

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
MNX1NM_005515.4 linkc.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 Appris UniProt
MNX1ENST00000252971.11 linkc.393_401dupCGCCGCCGC p.Ala132_Ala134dup disruptive_inframe_insertion Exon 1 of 3 1 NM_005515.4 ENSP00000252971.5 P50219-1
MNX1-AS1ENST00000818900.1 linkn.296+1925_296+1933dupGGCGGCGGC intron_variant Intron 1 of 1
MNX1-AS1ENST00000818901.1 linkn.50+840_50+848dupGGCGGCGGC intron_variant Intron 1 of 1

Frequencies

GnomAD3 genomes
AF:
0.105
AC:
13620
AN:
129580
Hom.:
1092
Cov.:
0
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.:
28
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:
89
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:
22
AN:
1338
Middle Eastern (MID)
AF:
0.0455
AC:
72
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
0
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
0
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.:
0
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:
6
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
0
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
0
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)

Splicing

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

Publications

Other links and lift over

dbSNP: rs548755417; hg19: chr7-156802643; COSMIC: COSV53318499; COSMIC: COSV53318499; API