2-151278901-C-T

Variant names:

• chr2-151278901-C-T
• rs11551174
• NM_004688.3:c.267G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_004688.3(NMI):​c.267G>A​(p.Ser89Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0641 in 1,612,616 control chromosomes in the GnomAD database, including 3,719 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S89S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.063 (357 hom., cov: 32)
  • Exomes 𝑓: 0.064 (3362 hom.)
• Consequence: NMI NM_004688.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239
• Publications: 15 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP7: Synonymous conserved (PhyloP=-0.239 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0753 is higher than 0.05.

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.267G>A	p.Ser89Ser	synonymous	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.267G>A	p.Ser89Ser	synonymous	Exon 4 of 8	ENSP00000243346.5	Q13287
	NMI	ENST00000883657.1		c.267G>A	p.Ser89Ser	synonymous	Exon 4 of 8	ENSP00000553716.1
	NMI	ENST00000883659.1		c.267G>A	p.Ser89Ser	synonymous	Exon 5 of 9	ENSP00000553718.1

Frequencies

GnomAD3 genomes AF: 0.0627 AC: 9537 AN: 152102 Hom.: 356 Cov.: 32

Gnomad AFR AF: 0.0547

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0758

Gnomad ASJ AF: 0.0570

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0821

Gnomad FIN AF: 0.0855

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0643

Gnomad OTH AF: 0.0612

GnomAD2 exomes AF: 0.0679 AC: 17037 AN: 250796 AF XY: 0.0679

Gnomad AFR exome AF: 0.0541

Gnomad AMR exome AF: 0.0989

Gnomad ASJ exome AF: 0.0573

Gnomad EAS exome AF: 0.000381

Gnomad FIN exome AF: 0.0845

Gnomad NFE exome AF: 0.0634

Gnomad OTH exome AF: 0.0616

GnomAD4 exome AF: 0.0643 AC: 93857 AN: 1460396 Hom.: 3362 Cov.: 30 AF XY: 0.0645 AC XY: 46882 AN XY: 726546

African (AFR) AF: 0.0519 AC: 1736 AN: 33456

American (AMR) AF: 0.0993 AC: 4437 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.0562 AC: 1466 AN: 26106

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39624

South Asian (SAS) AF: 0.0886 AC: 7637 AN: 86190

European-Finnish (FIN) AF: 0.0853 AC: 4545 AN: 53294

Middle Eastern (MID) AF: 0.0420 AC: 242 AN: 5758

European-Non Finnish (NFE) AF: 0.0631 AC: 70097 AN: 1110950

Other (OTH) AF: 0.0611 AC: 3687 AN: 60340

GnomAD4 genome AF: 0.0627 AC: 9539 AN: 152220 Hom.: 357 Cov.: 32 AF XY: 0.0629 AC XY: 4682 AN XY: 74436

African (AFR) AF: 0.0547 AC: 2270 AN: 41534

American (AMR) AF: 0.0755 AC: 1155 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0570 AC: 198 AN: 3472

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5188

South Asian (SAS) AF: 0.0820 AC: 396 AN: 4830

European-Finnish (FIN) AF: 0.0855 AC: 906 AN: 10592

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0643 AC: 4371 AN: 67996

Other (OTH) AF: 0.0605 AC: 128 AN: 2114

Alfa AF: 0.0608 Hom.: 673

Bravo AF: 0.0615

Asia WGS AF: 0.0330 AC: 113 AN: 3476

EpiCase AF: 0.0642

EpiControl AF: 0.0600

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	10
DANN	Benign	0.75
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11551174; hg19: chr2-152135415;