2-151270701-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004688.3(NMI):​c.916G>A​(p.Glu306Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000224 in 1,611,960 control chromosomes in the GnomAD database, including 2 homozygotes. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00023 ( 2 hom. )

Consequence

NMI
NM_004688.3 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.14
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 -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.088116735).
BS2
High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NMINM_004688.3 linkuse as main transcriptc.916G>A p.Glu306Lys missense_variant 8/8 ENST00000243346.10 NP_004679.2
NMIXM_047446270.1 linkuse as main transcriptc.1189G>A p.Glu397Lys missense_variant 8/8 XP_047302226.1
NMIXM_005246941.3 linkuse as main transcriptc.916G>A p.Glu306Lys missense_variant 8/8 XP_005246998.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NMIENST00000243346.10 linkuse as main transcriptc.916G>A p.Glu306Lys missense_variant 8/81 NM_004688.3 ENSP00000243346 P1

Frequencies

GnomAD3 genomes
AF:
0.000184
AC:
28
AN:
152186
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000264
AC:
66
AN:
250154
Hom.:
0
AF XY:
0.000348
AC XY:
47
AN XY:
135212
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000176
Gnomad ASJ exome
AF:
0.000299
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000659
Gnomad FIN exome
AF:
0.000139
Gnomad NFE exome
AF:
0.000282
Gnomad OTH exome
AF:
0.000328
GnomAD4 exome
AF:
0.000228
AC:
333
AN:
1459656
Hom.:
2
Cov.:
30
AF XY:
0.000249
AC XY:
181
AN XY:
726144
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000135
Gnomad4 ASJ exome
AF:
0.000230
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000652
Gnomad4 FIN exome
AF:
0.000131
Gnomad4 NFE exome
AF:
0.000213
Gnomad4 OTH exome
AF:
0.000282
GnomAD4 genome
AF:
0.000184
AC:
28
AN:
152304
Hom.:
0
Cov.:
33
AF XY:
0.000188
AC XY:
14
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000330
Hom.:
0
Bravo
AF:
0.000189
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000264
AC:
32
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.000328
EpiControl
AF:
0.000356

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 GeneticsMar 20, 2023The c.916G>A (p.E306K) alteration is located in exon 8 (coding exon 7) of the NMI gene. This alteration results from a G to A substitution at nucleotide position 916, causing the glutamic acid (E) at amino acid position 306 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
0.12
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.25
T
Eigen
Benign
-0.11
Eigen_PC
Benign
-0.063
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.52
T
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.088
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Pathogenic
3.0
M
MutationTaster
Benign
0.85
D
PrimateAI
Benign
0.47
T
PROVEAN
Uncertain
-2.6
D
REVEL
Benign
0.048
Sift
Benign
0.098
T
Sift4G
Benign
0.085
T
Polyphen
0.58
P
Vest4
0.27
MVP
0.63
MPC
0.072
ClinPred
0.12
T
GERP RS
3.2
Varity_R
0.088
gMVP
0.49

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: rs142057911; hg19: chr2-152127215; API