rs773751305

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004688.3(NMI):​c.677T>G​(p.Ile226Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,433,640 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 7.0e-7 ( 0 hom. )

Consequence

NMI
NM_004688.3 missense

Scores

5
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.444
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NMINM_004688.3 linkc.677T>G p.Ile226Arg missense_variant Exon 7 of 8 ENST00000243346.10 NP_004679.2 Q13287
NMIXM_047446270.1 linkc.950T>G p.Ile317Arg missense_variant Exon 7 of 8 XP_047302226.1
NMIXM_005246941.3 linkc.677T>G p.Ile226Arg missense_variant Exon 7 of 8 XP_005246998.1 Q13287

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NMIENST00000243346.10 linkc.677T>G p.Ile226Arg missense_variant Exon 7 of 8 1 NM_004688.3 ENSP00000243346.5 Q13287

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.98e-7
AC:
1
AN:
1433640
Hom.:
0
Cov.:
25
AF XY:
0.00
AC XY:
0
AN XY:
714700
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:
9.19e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.25
BayesDel_addAF
Benign
-0.062
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
20
DANN
Benign
0.97
DEOGEN2
Benign
0.15
T
Eigen
Benign
-0.33
Eigen_PC
Benign
-0.52
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.68
T
M_CAP
Benign
0.021
T
MetaRNN
Uncertain
0.70
D
MetaSVM
Benign
-0.94
T
MutationAssessor
Uncertain
2.7
M
PrimateAI
Benign
0.37
T
PROVEAN
Uncertain
-3.2
D
REVEL
Benign
0.13
Sift
Uncertain
0.027
D
Sift4G
Uncertain
0.016
D
Polyphen
0.94
P
Vest4
0.53
MutPred
0.68
Loss of sheet (P = 0.007);
MVP
0.49
MPC
0.29
ClinPred
0.78
D
GERP RS
-0.35
Varity_R
0.19
gMVP
0.76

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-152128204; API