GeneBe

rs548755417

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_005515.4(MNX1):​c.384_401delCGCCGCCGCCGCCGCCGC​(p.Ala129_Ala134del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000128 in 778,498 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A128A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 0)
Exomes 𝑓: 0.0000013 ( 0 hom. )

Consequence

MNX1
NM_005515.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.14

Publications

0 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))

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP3
Nonframeshift variant in repetitive region in NM_005515.4

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MNX1NM_005515.4 linkc.384_401delCGCCGCCGCCGCCGCCGC p.Ala129_Ala134del disruptive_inframe_deletion 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.384_401delCGCCGCCGCCGCCGCCGC p.Ala129_Ala134del disruptive_inframe_deletion Exon 1 of 3 1 NM_005515.4 ENSP00000252971.5 P50219-1
MNX1-AS1ENST00000818900.1 linkn.296+1916_296+1933delGGCGGCGGCGGCGGCGGC intron_variant Intron 1 of 1
MNX1-AS1ENST00000818901.1 linkn.50+831_50+848delGGCGGCGGCGGCGGCGGC intron_variant Intron 1 of 1

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD4 exome
AF:
0.00000128
AC:
1
AN:
778498
Hom.:
0
AF XY:
0.00000275
AC XY:
1
AN XY:
363730
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
14820
American (AMR)
AF:
0.00
AC:
0
AN:
1346
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
4992
East Asian (EAS)
AF:
0.00
AC:
0
AN:
4306
South Asian (SAS)
AF:
0.00
AC:
0
AN:
16176
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
1340
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
1586
European-Non Finnish (NFE)
AF:
0.00000141
AC:
1
AN:
707980
Other (OTH)
AF:
0.00
AC:
0
AN:
25952
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
3.1
Mutation Taster
=184/16
polymorphism

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; API