2-151270716-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.901C>T​(p.His301Tyr) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Consequence

NMI
NM_004688.3 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.517
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]

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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=0.03176424).
BP6
Variant 2-151270716-G-A is Benign according to our data. Variant chr2-151270716-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3200825.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.901C>T p.His301Tyr missense_variant 8/8 ENST00000243346.10 NP_004679.2
NMIXM_047446270.1 linkuse as main transcriptc.1174C>T p.His392Tyr missense_variant 8/8 XP_047302226.1
NMIXM_005246941.3 linkuse as main transcriptc.901C>T p.His301Tyr missense_variant 8/8 XP_005246998.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NMIENST00000243346.10 linkuse as main transcriptc.901C>T p.His301Tyr missense_variant 8/81 NM_004688.3 ENSP00000243346 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000312
Hom.:
0

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 GeneticsDec 08, 2023This 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
0.061
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.78
CADD
Benign
0.069
DANN
Benign
0.22
DEOGEN2
Benign
0.072
T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.015
N
LIST_S2
Benign
0.57
T
M_CAP
Benign
0.0046
T
MetaRNN
Benign
0.032
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.18
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.76
N
REVEL
Benign
0.045
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Polyphen
0.0
B
Vest4
0.059
MutPred
0.38
Loss of disorder (P = 0.0603);
MVP
0.23
MPC
0.040
ClinPred
0.024
T
GERP RS
-9.3
Varity_R
0.028
gMVP
0.43

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: rs1683167396; hg19: chr2-152127230; API