Genetic Variant NM_004688.3:c.47C>T (chr2-151282902-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 2P and 12B. PM1BP4_StrongBA1

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. 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.

Frequency

Genomes: 𝑓 0.36 ( 12045 hom., cov: 32)

Exomes 𝑓: 0.44 ( 138490 hom. )

Consequence

NMI
NM_004688.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.07

Publications

36 publications found

Variant links:

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]

NMI links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity NMI_HUMAN

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 rank	MANE	Protein
NMI	NM_004688.3 link	c.47C>T	p.Ser16Leu	missense_variant	Exon 2 of 8	ENST00000243346.10	NP_004679.2
NMI	XM_047446270.1 link	c.320C>T	p.Ser107Leu	missense_variant	Exon 2 of 8		XP_047302226.1
NMI	XM_005246941.3 link	c.47C>T	p.Ser16Leu	missense_variant	Exon 2 of 8		XP_005246998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
NMI	ENST00000243346.10 link	c.47C>T	p.Ser16Leu	missense_variant	Exon 2 of 8	1	NM_004688.3	ENSP00000243346.5
NMI	ENST00000414946.1 link	c.47C>T	p.Ser16Leu	missense_variant	Exon 3 of 4	5		ENSP00000387373.1
NMI	ENST00000477072.1 link	n.324C>T		non_coding_transcript_exon_variant	Exon 2 of 2	3
NMI	ENST00000491771.5 link	n.324C>T		non_coding_transcript_exon_variant	Exon 2 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.361

AC:

54781

AN:

151742

Hom.:

12034

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.422

AC:

89520

AN:

212222

AF XY:

0.418

show subpopulations

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 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.:

AF XY:

0.438

AC XY:

297392

AN XY:

678620

show subpopulations

African (AFR)

AF:

0.0875

AC:

2695

AN:

30796

American (AMR)

AF:

0.585

AC:

18463

AN:

31546

Ashkenazi Jewish (ASJ)

AF:

0.334

AC:

8138

AN:

24366

East Asian (EAS)

AF:

0.418

AC:

15411

AN:

36878

South Asian (SAS)

AF:

0.318

AC:

23356

AN:

73442

European-Finnish (FIN)

AF:

0.519

AC:

26987

AN:

51956

Middle Eastern (MID)

AF:

0.349

AC:

1712

AN:

4910

European-Non Finnish (NFE)

AF:

0.459

AC:

481861

AN:

1050522

Other (OTH)

AF:

0.406

AC:

22913

AN:

56410

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

13086

26172

39258

52344

65430

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14198

28396

42594

56792

70990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.361

AC:

54789

AN:

151860

Hom.:

12045

Cov.:

AF XY:

0.367

AC XY:

27267

AN XY:

74218

show subpopulations

African (AFR)

AF:

0.104

AC:

4321

AN:

41390

American (AMR)

AF:

0.506

AC:

7724

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.342

AC:

1188

AN:

3470

East Asian (EAS)

AF:

0.380

AC:

1964

AN:

5164

South Asian (SAS)

AF:

0.329

AC:

1584

AN:

4812

European-Finnish (FIN)

AF:

0.541

AC:

5675

AN:

10490

Middle Eastern (MID)

AF:

0.374

AC:

110

AN:

294

European-Non Finnish (NFE)

AF:

0.458

AC:

31106

AN:

67950

Other (OTH)

AF:

0.357

AC:

754

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1580

3160

4739

6319

7899

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

520

1040

1560

2080

2600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.412

Hom.:

41361

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

BayesDel_noAF

Benign

-0.50

CADD

Benign

0.0060

(source)

DANN

Benign

0.37

DEOGEN2

Benign

0.071

T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0090

LIST_S2

Benign

0.35

T;T

MetaRNN

Benign

0.000036

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

N;.

PhyloP100

-2.1

PrimateAI

Benign

0.25

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

GERP RS

-4.6

Varity_R

0.032

gMVP

0.095

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over