rs2276403

Positions:

• chr1-158847809-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 12/20 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. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.930

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MNDA	NM_002432.3	c.1069C>T	p.His357Tyr	missense_variant	6/7	ENST00000368141.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MNDA	ENST00000368141.5	c.1069C>T	p.His357Tyr	missense_variant	6/7	1	NM_002432.3	P1
MNDA	ENST00000438394.1	c.187C>T	p.His63Tyr	missense_variant	2/3	3

Frequencies

GnomAD3 genomes AF: 0.00274 AC: 417 AN: 152080 Hom.: 21 Cov.: 32

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

GnomAD3 exomes AF: 0.00607 AC: 1525 AN: 251342 Hom.: 67 AF XY: 0.00555 AC XY: 754 AN XY: 135832

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 SAS exome AF: 0.000849

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.: 92 Cov.: 31 AF XY: 0.00195 AC XY: 1420 AN XY: 727170

Gnomad4 AFR exome AF: 0.000209

Gnomad4 AMR exome AF: 0.000134

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0657

Gnomad4 SAS exome AF: 0.00106

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000135

Gnomad4 OTH exome AF: 0.00368

GnomAD4 genome AF: 0.00271 AC: 413 AN: 152198 Hom.: 21 Cov.: 32 AF XY: 0.00325 AC XY: 242 AN XY: 74424

Gnomad4 AFR AF: 0.0000963

Gnomad4 AMR AF: 0.000393

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0751

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00181 Hom.: 17

Bravo AF: 0.00274

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.00539 AC: 655

Asia WGS AF: 0.0240 AC: 83 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	4.8
DANN	Benign	0.87
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.79	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.047
Sift	Benign	0.19	T
Sift4G	Benign	0.45	T
Polyphen		0.93	P
Vest4		0.17
MVP		0.22
MPC		0.028
ClinPred		0.085	T
GERP RS		-2.1
Varity_R		0.086
gMVP		0.050

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

Other links and lift over

dbSNP: rs2276403; hg19: chr1-158817599;