2-151275541-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_004688.3(NMI):​c.577C>T​(p.Arg193Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000489 in 1,613,940 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

NMI
NM_004688.3 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.819
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 Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.038745224).
BP6
Variant 2-151275541-G-A is Benign according to our data. Variant chr2-151275541-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2234475.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NMINM_004688.3 linkuse as main transcriptc.577C>T p.Arg193Cys missense_variant 6/8 ENST00000243346.10 NP_004679.2
NMIXM_047446270.1 linkuse as main transcriptc.850C>T p.Arg284Cys missense_variant 6/8 XP_047302226.1
NMIXM_005246941.3 linkuse as main transcriptc.577C>T p.Arg193Cys missense_variant 6/8 XP_005246998.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NMIENST00000243346.10 linkuse as main transcriptc.577C>T p.Arg193Cys missense_variant 6/81 NM_004688.3 ENSP00000243346 P1

Frequencies

GnomAD3 genomes
AF:
0.0000395
AC:
6
AN:
152062
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000318
AC:
8
AN:
251472
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135908
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000527
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000499
AC:
73
AN:
1461878
Hom.:
0
Cov.:
31
AF XY:
0.0000523
AC XY:
38
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000594
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000395
AC:
6
AN:
152062
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74266
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000564
Hom.:
0
Bravo
AF:
0.0000378
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsJun 22, 2021This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.072
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.74
CADD
Benign
0.097
DANN
Benign
0.71
DEOGEN2
Benign
0.11
T
Eigen
Benign
-2.2
Eigen_PC
Benign
-2.3
FATHMM_MKL
Benign
0.0089
N
LIST_S2
Benign
0.33
T
M_CAP
Benign
0.0015
T
MetaRNN
Benign
0.039
T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
-1.1
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-1.7
N
REVEL
Benign
0.039
Sift
Benign
0.22
T
Sift4G
Benign
0.18
T
Polyphen
0.0010
B
Vest4
0.11
MVP
0.085
MPC
0.045
ClinPred
0.037
T
GERP RS
-11
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.041
gMVP
0.46

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: rs200999974; hg19: chr2-152132055; COSMIC: COSV54637611; COSMIC: COSV54637611; API