rs1554594329
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_005515.4(MNX1):c.53dupC(p.Arg19ThrfsTer37) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,416,418 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
MNX1
NM_005515.4 frameshift
NM_005515.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.78
Publications
0 publications found
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]
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 18 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 43 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 7-157010297-T-TG is Pathogenic according to our data. Variant chr7-157010297-T-TG is described in ClinVar as Pathogenic. ClinVar VariationId is 435883.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_005515.4. You can select a different transcript below to see updated ACMG assignments.
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.0000154 AC: 3AN: 194354 AF XY: 0.0000185 show subpopulations
GnomAD2 exomes
AF:
AC:
3
AN:
194354
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000141 AC: 2AN: 1416418Hom.: 0 Cov.: 33 AF XY: 0.00000142 AC XY: 1AN XY: 703824 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1416418
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
703824
show subpopulations
African (AFR)
AF:
AC:
0
AN:
29816
American (AMR)
AF:
AC:
1
AN:
41176
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
24740
East Asian (EAS)
AF:
AC:
0
AN:
35274
South Asian (SAS)
AF:
AC:
0
AN:
82004
European-Finnish (FIN)
AF:
AC:
0
AN:
49962
Middle Eastern (MID)
AF:
AC:
0
AN:
5296
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1090010
Other (OTH)
AF:
AC:
1
AN:
58140
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
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2
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
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<30
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
2
-
-
Currarino triad (2)
2
-
-
not provided (2)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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