Variant rs1048135 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_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. 13/20 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.07

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 made for transcript

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
NMI	NM_004688.3 linkuse as main transcript	c.47C>T	p.Ser16Leu	missense_variant	2/8	ENST00000243346.10
NMI	XM_047446270.1 linkuse as main transcript	c.320C>T	p.Ser107Leu	missense_variant	2/8
NMI	XM_005246941.3 linkuse as main transcript	c.47C>T	p.Ser16Leu	missense_variant	2/8

Ensembl

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

GnomAD3 exomes

AF:

0.422

AC:

89520

AN:

212222

Hom.:

20772

AF XY:

0.418

AC XY:

48558

AN XY:

116206

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 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.:

AF XY:

0.438

AC XY:

297392

AN XY:

678620

show subpopulations

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.:

AF XY:

0.367

AC XY:

27267

AN XY:

74218

show subpopulations

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

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

LIST_S2

Benign

0.35

T;T

MetaRNN

Benign

0.000036

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

N;.

MutationTaster

Benign

1.0

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over