2-151282024-G-C

Variant names:

• chr2-151282024-G-C
• rs1406318181
• NM_004688.3:c.101C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004688.3(NMI):​c.101C>G​(p.Thr34Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,924 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: NMI NM_004688.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.10

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06353915).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NMI	NM_004688.3	c.101C>G	p.Thr34Arg	missense_variant	Exon 3 of 8	ENST00000243346.10	NP_004679.2
NMI	XM_047446270.1	c.374C>G	p.Thr125Arg	missense_variant	Exon 3 of 8		XP_047302226.1
NMI	XM_005246941.3	c.101C>G	p.Thr34Arg	missense_variant	Exon 3 of 8		XP_005246998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NMI	ENST00000243346.10	c.101C>G	p.Thr34Arg	missense_variant	Exon 3 of 8	1	NM_004688.3	ENSP00000243346.5
NMI	ENST00000491771.5	n.358+844C>G		intron_variant	Intron 2 of 2	2
NMI	ENST00000414946.1	c.*15C>G		downstream_gene_variant		5		ENSP00000387373.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151924 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 21

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151924 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74178

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.0040
DANN	Benign	0.18
DEOGEN2	Benign	0.070	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.85	L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.024
Sift	Benign	0.61	T
Sift4G	Benign	0.54	T
Polyphen		0.0010	B
Vest4		0.16
MutPred		0.53		Gain of MoRF binding (P = 0.0162);
MVP		0.22
MPC		0.042
ClinPred		0.046	T
GERP RS		-5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.056
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

Other links and lift over

dbSNP: rs1406318181; hg19: chr2-152138538;