1-158847809-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002432.3(MNDA):c.1069C>T(p.His357Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00208 in 1,613,932 control chromosomes in the GnomAD database, including 113 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H357N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0027 ( 21 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 92 hom. )

Consequence

MNDA
NM_002432.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.930

Publications

11 publications found

Variant links:

Genes affected

MNDA (HGNC:7183): (myeloid cell nuclear differentiation antigen) The myeloid cell nuclear differentiation antigen (MNDA) is detected only in nuclei of cells of the granulocyte-monocyte lineage. A 200-amino acid region of human MNDA is strikingly similar to a region in the proteins encoded by a family of interferon-inducible mouse genes, designated Ifi-201, Ifi-202, and Ifi-203, that are not regulated in a cell- or tissue-specific fashion. The 1.8-kb MNDA mRNA, which contains an interferon-stimulated response element in the 5-prime untranslated region, was significantly upregulated in human monocytes exposed to interferon alpha. MNDA is located within 2,200 kb of FCER1A, APCS, CRP, and SPTA1. In its pattern of expression and/or regulation, MNDA resembles IFI16, suggesting that these genes participate in blood cell-specific responses to interferons. [provided by RefSeq, Jul 2008]

MNDA links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_002432.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001929611).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.069 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002432.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MNDA	NM_002432.3	MANE Select	c.1069C>T	p.His357Tyr	missense	Exon 6 of 7	NP_002423.1	P41218

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MNDA	ENST00000368141.5	TSL:1 MANE Select	c.1069C>T	p.His357Tyr	missense	Exon 6 of 7	ENSP00000357123.4	P41218
MNDA	ENST00000963511.1		c.1102C>T	p.His368Tyr	missense	Exon 6 of 7	ENSP00000633570.1
MNDA	ENST00000963510.1		c.901C>T	p.His301Tyr	missense	Exon 5 of 6	ENSP00000633569.1

Frequencies

GnomAD3 genomes

AF:

0.00274

AC:

417

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0757

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00607

AC:

1525

AN:

251342

AF XY:

0.00555

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000173

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0801

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00202

AC:

2950

AN:

1461734

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

1420

AN XY:

727170

show subpopulations

African (AFR)

AF:

0.000209

AC:

AN:

33476

American (AMR)

AF:

0.000134

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.0657

AC:

2608

AN:

39688

South Asian (SAS)

AF:

0.00106

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000135

AC:

AN:

1111886

Other (OTH)

AF:

0.00368

AC:

222

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

153

306

458

611

764

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

156

208

260

<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:

0.00271

AC:

413

AN:

152198

Hom.:

Cov.:

AF XY:

0.00325

AC XY:

242

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0000963

AC:

AN:

41540

American (AMR)

AF:

0.000393

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0751

AC:

388

AN:

5164

South Asian (SAS)

AF:

0.00166

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68000

Other (OTH)

AF:

0.00237

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00139

Hom.:

Bravo

AF:

0.00274

Asia WGS

AF:

0.0240

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.56

CADD

Benign

4.8

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.024

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.79

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

PhyloP100

-0.93

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.047

Sift

Benign

0.19

Sift4G

Benign

0.45

Varity_R

0.086

gMVP

0.050

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over