Genetic Variant NMI:p.Gln39His (chr2-151282008-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004688.3(NMI):c.117A>T(p.Gln39His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NMI
NM_004688.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.69

Publications

27 publications found

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]

NMI links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.102283835).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004688.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NMI	NM_004688.3	MANE Select	c.117A>T	p.Gln39His	missense	Exon 3 of 8	NP_004679.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NMI	ENST00000243346.10	TSL:1 MANE Select	c.117A>T	p.Gln39His	missense	Exon 3 of 8	ENSP00000243346.5
NMI	ENST00000491771.5	TSL:2	n.358+860A>T		intron	N/A
NMI	ENST00000414946.1	TSL:5	c.*31A>T		downstream_gene	N/A	ENSP00000387373.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1387504

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

694232

African (AFR)

AF:

0.00

AC:

AN:

31702

American (AMR)

AF:

0.00

AC:

AN:

43226

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25666

East Asian (EAS)

AF:

0.00

AC:

AN:

39248

South Asian (SAS)

AF:

0.00

AC:

AN:

82754

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53360

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5600

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1047996

Other (OTH)

AF:

0.00

AC:

AN:

57952

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.36

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.13

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.47

M_CAP

Benign

0.0061

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.4

PhyloP100

-1.7

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.8

REVEL

Benign

0.027

Sift

Benign

0.076

Sift4G

Uncertain

0.054

Polyphen

0.0080

Vest4

0.12

MutPred

0.42

Loss of helix (P = 0.0558)

MVP

0.28

MPC

0.037

ClinPred

0.062

GERP RS

-5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.049

gMVP

0.18

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over