2-151275564-C-T

Variant summary

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

The NM_004688.3(NMI):​c.554G>A​(p.Arg185Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,614,178 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 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

NMI
NM_004688.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.140
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=0.024340898).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NMINM_004688.3 linkuse as main transcriptc.554G>A p.Arg185Gln missense_variant 6/8 ENST00000243346.10 NP_004679.2
NMIXM_047446270.1 linkuse as main transcriptc.827G>A p.Arg276Gln missense_variant 6/8 XP_047302226.1
NMIXM_005246941.3 linkuse as main transcriptc.554G>A p.Arg185Gln missense_variant 6/8 XP_005246998.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NMIENST00000243346.10 linkuse as main transcriptc.554G>A p.Arg185Gln missense_variant 6/81 NM_004688.3 ENSP00000243346 P1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152172
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000770
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000636
AC:
16
AN:
251480
Hom.:
0
AF XY:
0.0000662
AC XY:
9
AN XY:
135912
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000598
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000226
AC:
33
AN:
1461888
Hom.:
0
Cov.:
31
AF XY:
0.0000206
AC XY:
15
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000327
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000525
AC:
8
AN:
152290
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000771
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000564
Hom.:
0
Bravo
AF:
0.0000491
ExAC
AF:
0.0000741
AC:
9
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 GeneticsFeb 27, 2023The c.554G>A (p.R185Q) alteration is located in exon 6 (coding exon 5) of the NMI gene. This alteration results from a G to A substitution at nucleotide position 554, causing the arginine (R) at amino acid position 185 to be replaced by a glutamine (Q). 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
0.099
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
13
DANN
Benign
0.90
DEOGEN2
Benign
0.083
T
Eigen
Benign
-0.65
Eigen_PC
Benign
-0.72
FATHMM_MKL
Benign
0.026
N
LIST_S2
Benign
0.74
T
M_CAP
Benign
0.027
D
MetaRNN
Benign
0.024
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.2
M
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-0.40
N
REVEL
Benign
0.042
Sift
Benign
0.27
T
Sift4G
Benign
0.44
T
Polyphen
0.52
P
Vest4
0.15
MVP
0.68
MPC
0.080
ClinPred
0.030
T
GERP RS
2.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.044
gMVP
0.35

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs201563970; hg19: chr2-152132078; API