Variant chr2-151275840-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004688.3(NMI):c.365G>A(p.Ser122Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000483 in 1,449,658 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

NMI
NM_004688.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.265

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 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=0.09713262).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NMI	NM_004688.3 linkuse as main transcript	c.365G>A	p.Ser122Asn	missense_variant	5/8	ENST00000243346.10	NP_004679.2
NMI	XM_047446270.1 linkuse as main transcript	c.638G>A	p.Ser213Asn	missense_variant	5/8		XP_047302226.1
NMI	XM_005246941.3 linkuse as main transcript	c.365G>A	p.Ser122Asn	missense_variant	5/8		XP_005246998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NMI	ENST00000243346.10 linkuse as main transcript	c.365G>A	p.Ser122Asn	missense_variant	5/8	1	NM_004688.3	ENSP00000243346	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000288

AC:

AN:

242766

Hom.:

AF XY:

0.00

AC XY:

AN XY:

130844

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000215

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000483

AC:

AN:

1449658

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720552

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000164

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000247

AC:

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 submitter

clinical testing

Ambry Genetics

Oct 03, 2022

The c.365G>A (p.S122N) alteration is located in exon 5 (coding exon 4) of the NMI gene. This alteration results from a G to A substitution at nucleotide position 365, causing the serine (S) at amino acid position 122 to be replaced by an asparagine (N). 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

0.074

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.73

CADD

Benign

9.1

DANN

Benign

0.96

DEOGEN2

Benign

0.076

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.61

M_CAP

Benign

0.013

MetaRNN

Benign

0.097

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.46

REVEL

Benign

0.039

Sift

Benign

0.083

Sift4G

Benign

0.33

Polyphen

0.36

Vest4

0.19

MutPred

0.40

Loss of catalytic residue at K123 (P = 0.0423);

MVP

0.50

MPC

0.057

ClinPred

0.023

GERP RS

0.58

Varity_R

0.040

gMVP

0.21

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over