Genetic Variant NMI:p.Ser89Ser (chr2-151278901-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

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.

Frequency

Genomes: 𝑓 0.063 ( 357 hom., cov: 32)

Exomes 𝑓: 0.064 ( 3362 hom. )

Consequence

NMI
NM_004688.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.239

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NMI	NM_004688.3 link	c.267G>A	p.Ser89Ser	synonymous_variant	Exon 4 of 8	ENST00000243346.10	NP_004679.2	Q13287
NMI	XM_047446270.1 link	c.540G>A	p.Ser180Ser	synonymous_variant	Exon 4 of 8		XP_047302226.1
NMI	XM_005246941.3 link	c.267G>A	p.Ser89Ser	synonymous_variant	Exon 4 of 8		XP_005246998.1	Q13287

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NMI	ENST00000243346.10 link	c.267G>A	p.Ser89Ser	synonymous_variant	Exon 4 of 8	1	NM_004688.3	ENSP00000243346.5		Q13287
NMI	ENST00000491771.5 link	n.448G>A		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.0627

AC:

9537

AN:

152102

Hom.:

356

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0679

AC:

17037

AN:

250796

Hom.:

687

AF XY:

0.0679

AC XY:

9204

AN XY:

135576

show subpopulations

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 SAS exome

AF:

0.0906

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.:

AF XY:

0.0645

AC XY:

46882

AN XY:

726546

show subpopulations

Gnomad4 AFR exome

AF:

0.0519

Gnomad4 AMR exome

AF:

0.0993

Gnomad4 ASJ exome

AF:

0.0562

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.0886

Gnomad4 FIN exome

AF:

0.0853

Gnomad4 NFE exome

AF:

0.0631

Gnomad4 OTH exome

AF:

0.0611

GnomAD4 genome

AF:

0.0627

AC:

9539

AN:

152220

Hom.:

357

Cov.:

AF XY:

0.0629

AC XY:

4682

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0547

Gnomad4 AMR

AF:

0.0755

Gnomad4 ASJ

AF:

0.0570

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.0820

Gnomad4 FIN

AF:

0.0855

Gnomad4 NFE

AF:

0.0643

Gnomad4 OTH

AF:

0.0605

Alfa

AF:

0.0605

Hom.:

491

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.75

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

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