rs369277204
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_005515.4(MNX1):c.975G>A(p.Ala325=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,609,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
MNX1
NM_005515.4 synonymous
NM_005515.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.36
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 made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
?
Variant 7-157005751-C-T is Benign according to our data. Variant chr7-157005751-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 435881.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-3.36 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0000853 (13/152322) while in subpopulation AFR AF= 0.000289 (12/41574). AF 95% confidence interval is 0.000166. There are 0 homozygotes in gnomad4. There are 8 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High AC in GnomAd at 12 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MNX1 | NM_005515.4 | c.975G>A | p.Ala325= | synonymous_variant | 3/3 | ENST00000252971.11 | |
MNX1 | NM_001165255.2 | c.339G>A | p.Ala113= | synonymous_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MNX1 | ENST00000252971.11 | c.975G>A | p.Ala325= | synonymous_variant | 3/3 | 1 | NM_005515.4 | P2 | |
MNX1 | ENST00000543409.5 | c.339G>A | p.Ala113= | synonymous_variant | 3/3 | 1 | A2 | ||
MNX1 | ENST00000469500.5 | c.55+3247G>A | intron_variant | 1 | |||||
MNX1 | ENST00000479817.1 | c.38+3909G>A | intron_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000788 AC: 12AN: 152212Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000168 AC: 4AN: 238266Hom.: 0 AF XY: 0.0000153 AC XY: 2AN XY: 130976
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GnomAD4 exome AF: 0.00000755 AC: 11AN: 1457028Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2AN XY: 724812
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GnomAD4 genome ? AF: 0.0000853 AC: 13AN: 152322Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8AN XY: 74486
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 25, 2016 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 18, 2022 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at