2-151270875-T-C

Variant names:

• chr2-151270875-T-C
• rs367578406
• NM_004688.3:c.742A>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.742A>G​(p.Ile248Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000757 in 1,453,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000076 (0 hom.)
• Consequence: NMI NM_004688.3 missense, splice_region
• Scores: Splicing: ADA: 0.00002994
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.860

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=0.016509593).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NMI	NM_004688.3	c.742A>G	p.Ile248Val	missense_variant, splice_region_variant	Exon 8 of 8	ENST00000243346.10	NP_004679.2
NMI	XM_047446270.1	c.1015A>G	p.Ile339Val	missense_variant, splice_region_variant	Exon 8 of 8		XP_047302226.1
NMI	XM_005246941.3	c.742A>G	p.Ile248Val	missense_variant, splice_region_variant	Exon 8 of 8		XP_005246998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NMI	ENST00000243346.10	c.742A>G	p.Ile248Val	missense_variant, splice_region_variant	Exon 8 of 8	1	NM_004688.3	ENSP00000243346.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000407 AC: 10 AN: 245848 Hom.: 0 AF XY: 0.0000451 AC XY: 6 AN XY: 133006

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000304

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000757 AC: 11 AN: 1453660 Hom.: 0 Cov.: 28 AF XY: 0.00000968 AC XY: 7 AN XY: 723158

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000209

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000264

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.012
DANN	Benign	0.22
DEOGEN2	Benign	0.071	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0078	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-2.1	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.25	N
REVEL	Benign	0.013
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.027
MutPred		0.33		Gain of MoRF binding (P = 0.1331);
MVP		0.16
MPC		0.033
ClinPred		0.015	T
GERP RS		-0.61
Varity_R		0.012
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000030
dbscSNV1_RF	Benign	0.052
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: rs367578406; hg19: chr2-152127389;