NM_004688.3:c.360C>A

Variant names:

• chr2-151275845-G-T
• NM_004688.3:c.360C>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_004688.3(NMI):​c.360C>A​(p.Ser120Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NMI NM_004688.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0330

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060400277).
• BP6: Variant 2-151275845-G-T is Benign according to our data. Variant chr2-151275845-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2608123.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NMI	NM_004688.3	c.360C>A	p.Ser120Arg	missense_variant	Exon 5 of 8	ENST00000243346.10	NP_004679.2
NMI	XM_047446270.1	c.633C>A	p.Ser211Arg	missense_variant	Exon 5 of 8		XP_047302226.1
NMI	XM_005246941.3	c.360C>A	p.Ser120Arg	missense_variant	Exon 5 of 8		XP_005246998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NMI	ENST00000243346.10	c.360C>A	p.Ser120Arg	missense_variant	Exon 5 of 8	1	NM_004688.3	ENSP00000243346.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jun 29, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.43
DANN	Benign	0.14
DEOGEN2	Benign	0.067	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0054	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.5	N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.041
Sift	Benign	0.62	T
Sift4G	Benign	0.90	T
Polyphen		0.0	B
Vest4		0.22
MutPred		0.49		Gain of MoRF binding (P = 0.0065);
MVP		0.36
MPC		0.040
ClinPred		0.030	T
GERP RS		-1.6
Varity_R		0.028
gMVP		0.22

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-152132359;