rs1048135

chr2-151282902-G-Achr2-151282902-G-Cchr2-151282902-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004688.3(NMI):c.47C>T(p.Ser16Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 1,512,686 control chromosomes in the GnomAD database, including 150,535 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.36 (12045 hom., cov: 32)
  • Exomes 𝑓: 0.44 (138490 hom.)
• 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.6276535E-5).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NMI	NM_004688.3	c.47C>T	p.Ser16Leu	missense_variant	2/8	ENST00000243346.10
NMI	XM_047446270.1	c.320C>T	p.Ser107Leu	missense_variant	2/8
NMI	XM_005246941.3	c.47C>T	p.Ser16Leu	missense_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NMI	ENST00000243346.10	c.47C>T	p.Ser16Leu	missense_variant	2/8	1	NM_004688.3	P1
NMI	ENST00000414946.1	c.47C>T	p.Ser16Leu	missense_variant	3/4	5
NMI	ENST00000477072.1	n.324C>T		non_coding_transcript_exon_variant	2/2	3
NMI	ENST00000491771.5	n.324C>T		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54781 AN: 151742 Hom.: 12034 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.362

GnomAD3 exomes AF: 0.422 AC: 89520 AN: 212222 Hom.: 20772 AF XY: 0.418 AC XY: 48558 AN XY: 116206

Gnomad AFR exome AF: 0.0953

Gnomad AMR exome AF: 0.603

Gnomad ASJ exome AF: 0.331

Gnomad EAS exome AF: 0.373

Gnomad SAS exome AF: 0.320

Gnomad FIN exome AF: 0.526

Gnomad NFE exome AF: 0.446

Gnomad OTH exome AF: 0.432

GnomAD4 exome AF: 0.442 AC: 601536 AN: 1360826 Hom.: 138490 Cov.: 25 AF XY: 0.438 AC XY: 297392 AN XY: 678620

Gnomad4 AFR exome AF: 0.0875

Gnomad4 AMR exome AF: 0.585

Gnomad4 ASJ exome AF: 0.334

Gnomad4 EAS exome AF: 0.418

Gnomad4 SAS exome AF: 0.318

Gnomad4 FIN exome AF: 0.519

Gnomad4 NFE exome AF: 0.459

Gnomad4 OTH exome AF: 0.406

GnomAD4 genome AF: 0.361 AC: 54789 AN: 151860 Hom.: 12045 Cov.: 32 AF XY: 0.367 AC XY: 27267 AN XY: 74218

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.506

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.541

Gnomad4 NFE AF: 0.458

Gnomad4 OTH AF: 0.357

Alfa AF: 0.426 Hom.: 30296

Bravo AF: 0.349

TwinsUK AF: 0.487 AC: 1806

ALSPAC AF: 0.474 AC: 1826

ESP6500AA AF: 0.108 AC: 473

ESP6500EA AF: 0.448 AC: 3835

ExAC AF: 0.415 AC: 50354

Asia WGS AF: 0.315 AC: 1092 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	0.0060
Dann	Benign	0.37
DEOGEN2	Benign	0.071	T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0090	N
LIST_S2	Benign	0.35	T;T
MetaRNN	Benign	0.000036	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N;.
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.42	N;D
REVEL	Benign	0.11
Sift	Benign	0.68	T;.
Sift4G	Benign	0.66	T;.
Polyphen		0.0	B;B
Vest4		0.047
MPC		0.034
ClinPred		0.0019	T
GERP RS		-4.6
Varity_R		0.032
gMVP		0.095

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; COSMIC: COSV54638715;