NM_004688.3:c.47C>G

Variant names:

• chr2-151282902-G-C
• rs1048135
• NM_004688.3:c.47C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 4P and 4B. PM1 PM2 BP4_Strong

The NM_004688.3(NMI):​c.47C>G​(p.Ser16Trp) 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. 15/22 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)
• Consequence: NMI NM_004688.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07
• Publications: 36 publications found

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

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

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity NMI_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048385203).

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.47C>G	p.Ser16Trp	missense	Exon 2 of 8	NP_004679.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NMI	ENST00000243346.10	TSL:1 MANE Select	c.47C>G	p.Ser16Trp	missense	Exon 2 of 8	ENSP00000243346.5
	NMI	ENST00000414946.1	TSL:5	c.47C>G	p.Ser16Trp	missense	Exon 3 of 4	ENSP00000387373.1
	NMI	ENST00000477072.1	TSL:3	n.324C>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	0.023
DANN	Benign	0.23
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0042	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.90	N
PhyloP100		-2.1
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.15
Sift	Benign	0.21	T
Sift4G	Benign	0.14	T
Polyphen		0.0	B
Vest4		0.18
MutPred		0.17		Gain of catalytic residue at S16 (P = 0.0023)
MVP		0.45
MPC		0.045
ClinPred		0.074	T
GERP RS		-4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.037
gMVP		0.16
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs1048135; hg19: chr2-152139416;