rs773751305

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004688.3(NMI):ā€‹c.677T>Cā€‹(p.Ile226Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,190 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)

Consequence

NMI
NM_004688.3 missense

Scores

19

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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.119002104).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NMINM_004688.3 linkc.677T>C p.Ile226Thr missense_variant Exon 7 of 8 ENST00000243346.10 NP_004679.2 Q13287
NMIXM_047446270.1 linkc.950T>C p.Ile317Thr missense_variant Exon 7 of 8 XP_047302226.1
NMIXM_005246941.3 linkc.677T>C p.Ile226Thr 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>C p.Ile226Thr missense_variant Exon 7 of 8 1 NM_004688.3 ENSP00000243346.5 Q13287

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152190
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
25
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152190
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
13
DANN
Benign
0.30
DEOGEN2
Benign
0.089
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.058
N
LIST_S2
Benign
0.63
T
M_CAP
Benign
0.0056
T
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.0
L
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-0.87
N
REVEL
Benign
0.077
Sift
Benign
0.49
T
Sift4G
Benign
0.33
T
Polyphen
0.0040
B
Vest4
0.19
MutPred
0.66
Loss of sheet (P = 0.007);
MVP
0.25
MPC
0.048
ClinPred
0.048
T
GERP RS
-0.35
Varity_R
0.033
gMVP
0.56

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: rs773751305; hg19: chr2-152128204; API