2-151275582-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_004688.3(NMI):āc.536T>Cā(p.Leu179Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000682 in 1,614,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 32)
Exomes š: 0.0000062 ( 0 hom. )
Consequence
NMI
NM_004688.3 missense
NM_004688.3 missense
Scores
5
9
5
Clinical Significance
Conservation
PhyloP100: 6.87
Genes affected
NMI (HGNC:7854): (N-myc and STAT interactor) NMYC interactor (NMI) encodes a protein that interacts with NMYC and CMYC (two members of the oncogene Myc family), and other transcription factors containing a Zip, HLH, or HLH-Zip motif. The NMI protein also interacts with all STATs except STAT2 and augments STAT-mediated transcription in response to cytokines IL2 and IFN-gamma. The NMI mRNA has low expression levels in all human fetal and adult tissues tested except brain and has high expression in cancer cell line-myeloid leukemias. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.929
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NMI | NM_004688.3 | c.536T>C | p.Leu179Pro | missense_variant | 6/8 | ENST00000243346.10 | NP_004679.2 | |
NMI | XM_047446270.1 | c.809T>C | p.Leu270Pro | missense_variant | 6/8 | XP_047302226.1 | ||
NMI | XM_005246941.3 | c.536T>C | p.Leu179Pro | missense_variant | 6/8 | XP_005246998.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NMI | ENST00000243346.10 | c.536T>C | p.Leu179Pro | missense_variant | 6/8 | 1 | NM_004688.3 | ENSP00000243346 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152202Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251478Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135910
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461864Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727236
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152202Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74352
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 04, 2024 | The c.536T>C (p.L179P) alteration is located in exon 6 (coding exon 5) of the NMI gene. This alteration results from a T to C substitution at nucleotide position 536, causing the leucine (L) at amino acid position 179 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Benign
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MutPred
Loss of sheet (P = 0.0054);
MVP
MPC
ClinPred
D
GERP RS
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