2-151278925-G-C

Variant names:

• chr2-151278925-G-C
• rs1005983372
• NM_004688.3:c.243C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004688.3(NMI):​c.243C>G​(p.Ser81Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,611,474 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: NMI NM_004688.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.109
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048742086).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NMI	NM_004688.3	MANE Select	c.243C>G	p.Ser81Arg	missense	Exon 4 of 8	NP_004679.2	Q13287

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NMI	ENST00000243346.10	TSL:1 MANE Select	c.243C>G	p.Ser81Arg	missense	Exon 4 of 8	ENSP00000243346.5	Q13287
	NMI	ENST00000883657.1		c.243C>G	p.Ser81Arg	missense	Exon 4 of 8	ENSP00000553716.1
	NMI	ENST00000883659.1		c.243C>G	p.Ser81Arg	missense	Exon 5 of 9	ENSP00000553718.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152158 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

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 AF: 0.00000274 AC: 4 AN: 1459316 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726106

African (AFR) AF: 0.00 AC: 0 AN: 33432

American (AMR) AF: 0.0000895 AC: 4 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39612

South Asian (SAS) AF: 0.00 AC: 0 AN: 86190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109920

Other (OTH) AF: 0.00 AC: 0 AN: 60288

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152158 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74338

African (AFR) AF: 0.00 AC: 0 AN: 41432

American (AMR) AF: 0.000197 AC: 3 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Benign	0.93
DEOGEN2	Benign	0.078	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.11
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.070
Sift	Benign	0.45	T
Sift4G	Benign	0.57	T
Polyphen		0.0070	B
Vest4		0.12
MutPred		0.46		Loss of disorder (P = 0.0833)
MVP		0.38
MPC		0.041
ClinPred		0.077	T
GERP RS		2.3
Varity_R		0.030
gMVP		0.20
Mutation Taster		=89/11	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: rs1005983372; hg19: chr2-152135439;