2-151282902-G-C

Position:

• chr2-151282902-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S16L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NMI NM_004688.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07

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=0.048385203).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NMI	NM_004688.3	c.47C>G	p.Ser16Trp	missense_variant	2/8	ENST00000243346.10	NP_004679.2
NMI	XM_047446270.1	c.320C>G	p.Ser107Trp	missense_variant	2/8		XP_047302226.1
NMI	XM_005246941.3	c.47C>G	p.Ser16Trp	missense_variant	2/8		XP_005246998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NMI	ENST00000243346.10	c.47C>G	p.Ser16Trp	missense_variant	2/8	1	NM_004688.3	ENSP00000243346	P1
NMI	ENST00000414946.1	c.47C>G	p.Ser16Trp	missense_variant	3/4	5		ENSP00000387373
NMI	ENST00000477072.1	n.324C>G		non_coding_transcript_exon_variant	2/2	3
NMI	ENST00000491771.5	n.324C>G		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.048	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.90	N;.
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.15
Sift	Benign	0.21	T;.
Sift4G	Benign	0.14	T;.
Polyphen		0.0	B;B
Vest4		0.18
MutPred		0.17		Gain of catalytic residue at S16 (P = 0.0023);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

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

Other links and lift over

dbSNP: rs1048135; hg19: chr2-152139416;