chr2-151282024-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004688.3(NMI):​c.101C>A​(p.Thr34Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000672 in 1,487,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000067 ( 0 hom. )

Consequence

NMI
NM_004688.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.10
Variant links:
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]

Genome browser will be placed here

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;
BP4
Computational evidence support a benign effect (MetaRNN=0.058317393).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NMINM_004688.3 linkuse as main transcriptc.101C>A p.Thr34Lys missense_variant 3/8 ENST00000243346.10 NP_004679.2
NMIXM_047446270.1 linkuse as main transcriptc.374C>A p.Thr125Lys missense_variant 3/8 XP_047302226.1
NMIXM_005246941.3 linkuse as main transcriptc.101C>A p.Thr34Lys missense_variant 3/8 XP_005246998.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NMIENST00000243346.10 linkuse as main transcriptc.101C>A p.Thr34Lys missense_variant 3/81 NM_004688.3 ENSP00000243346 P1
NMIENST00000491771.5 linkuse as main transcriptn.358+844C>A intron_variant, non_coding_transcript_variant 2
NMIENST00000414946.1 linkuse as main transcript downstream_gene_variant 5 ENSP00000387373

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151924
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000820
AC:
2
AN:
243794
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
131748
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000179
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000674
AC:
9
AN:
1335630
Hom.:
0
Cov.:
21
AF XY:
0.00000298
AC XY:
2
AN XY:
670956
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000799
Gnomad4 OTH exome
AF:
0.0000178
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151924
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74178
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
EpiCase
AF:
0.0000547
EpiControl
AF:
0.0000596

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 submitterclinical testingAmbry GeneticsDec 02, 2021The c.101C>A (p.T34K) alteration is located in exon 3 (coding exon 2) of the NMI gene. This alteration results from a C to A substitution at nucleotide position 101, causing the threonine (T) at amino acid position 34 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.082
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
0.0020
DANN
Benign
0.16
DEOGEN2
Benign
0.068
T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.0092
N
LIST_S2
Benign
0.29
T
M_CAP
Benign
0.0051
T
MetaRNN
Benign
0.058
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
0.20
N
REVEL
Benign
0.039
Sift
Benign
0.91
T
Sift4G
Benign
0.91
T
Polyphen
0.017
B
Vest4
0.14
MutPred
0.56
Gain of ubiquitination at T34 (P = 0.0258);
MVP
0.22
MPC
0.042
ClinPred
0.062
T
GERP RS
-5.3
Varity_R
0.032
gMVP
0.16

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1406318181; hg19: chr2-152138538; API