6-89653113-T-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 3P and 5B. PM2PP2BP4_StrongBP6
The NM_014611.3(MDN1):c.15704A>C(p.Glu5235Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000644 in 1,614,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00035 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000034 ( 0 hom. )
Consequence
MDN1
NM_014611.3 missense
NM_014611.3 missense
Scores
1
2
15
Clinical Significance
Conservation
PhyloP100: 5.66
Genes affected
MDN1 (HGNC:18302): (midasin AAA ATPase 1) Predicted to enable ATP binding activity. Involved in ribosomal large subunit assembly. Located in cytosol; intermediate filament cytoskeleton; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, MDN1
BP4
?
Computational evidence support a benign effect (MetaRNN=0.045046955).
BP6
?
Variant 6-89653113-T-G is Benign according to our data. Variant chr6-89653113-T-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 3046141.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MDN1 | NM_014611.3 | c.15704A>C | p.Glu5235Ala | missense_variant | 94/102 | ENST00000369393.8 | |
MDN1-AS1 | NR_111915.1 | n.105+14477T>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MDN1 | ENST00000369393.8 | c.15704A>C | p.Glu5235Ala | missense_variant | 94/102 | 1 | NM_014611.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000348 AC: 53AN: 152182Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000955 AC: 24AN: 251244Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135780
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GnomAD4 exome AF: 0.0000342 AC: 50AN: 1461760Hom.: 0 Cov.: 31 AF XY: 0.0000275 AC XY: 20AN XY: 727170
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GnomAD4 genome ? AF: 0.000355 AC: 54AN: 152300Hom.: 0 Cov.: 33 AF XY: 0.000322 AC XY: 24AN XY: 74490
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 03, 2022 | The c.15704A>C (p.E5235A) alteration is located in exon 94 (coding exon 94) of the MDN1 gene. This alteration results from a A to C substitution at nucleotide position 15704, causing the glutamic acid (E) at amino acid position 5235 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
MDN1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 06, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;.
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;.
REVEL
Benign
Sift
Benign
T;.
Polyphen
P;P
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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