chr2-151275763-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_004688.3(NMI):ā€‹c.442T>Gā€‹(p.Phe148Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000174 in 1,612,582 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000026 ( 0 hom., cov: 32)
Exomes š‘“: 0.000016 ( 1 hom. )

Consequence

NMI
NM_004688.3 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.94
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.75

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NMINM_004688.3 linkuse as main transcriptc.442T>G p.Phe148Val missense_variant 5/8 ENST00000243346.10 NP_004679.2
NMIXM_047446270.1 linkuse as main transcriptc.715T>G p.Phe239Val missense_variant 5/8 XP_047302226.1
NMIXM_005246941.3 linkuse as main transcriptc.442T>G p.Phe148Val missense_variant 5/8 XP_005246998.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NMIENST00000243346.10 linkuse as main transcriptc.442T>G p.Phe148Val missense_variant 5/81 NM_004688.3 ENSP00000243346 P1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152210
Hom.:
0
Cov.:
32
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:
0.000621
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000478
AC:
12
AN:
251076
Hom.:
1
AF XY:
0.0000663
AC XY:
9
AN XY:
135720
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000360
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000164
AC:
24
AN:
1460372
Hom.:
1
Cov.:
30
AF XY:
0.0000234
AC XY:
17
AN XY:
726640
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:
0.000255
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152210
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74358
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:
0.000621
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.0000576
AC:
7
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 GeneticsMar 31, 2024The c.442T>G (p.F148V) alteration is located in exon 5 (coding exon 4) of the NMI gene. This alteration results from a T to G substitution at nucleotide position 442, causing the phenylalanine (F) at amino acid position 148 to be replaced by a valine (V). 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
Uncertain
0.54
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.16
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.16
T
Eigen
Uncertain
0.51
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.73
T
M_CAP
Benign
0.037
D
MetaRNN
Pathogenic
0.75
D
MetaSVM
Benign
-0.82
T
MutationAssessor
Benign
2.0
M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.61
T
PROVEAN
Uncertain
-3.7
D
REVEL
Benign
0.26
Sift
Uncertain
0.0040
D
Sift4G
Benign
0.81
T
Polyphen
1.0
D
Vest4
0.84
MutPred
0.65
Gain of MoRF binding (P = 0.0806);
MVP
0.74
MPC
0.26
ClinPred
0.68
D
GERP RS
4.3
Varity_R
0.35
gMVP
0.66

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: rs769692116; hg19: chr2-152132277; API