chr1-158842207-T-A

Position:

• chr1-158842207-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002432.3(MNDA):​c.54T>A​(p.Asp18Glu) 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D18Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MNDA NM_002432.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.239

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22400385).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MNDA	NM_002432.3	c.54T>A	p.Asp18Glu	missense_variant	2/7	ENST00000368141.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MNDA	ENST00000368141.5	c.54T>A	p.Asp18Glu	missense_variant	2/7	1	NM_002432.3	P1
MNDA	ENST00000491210.1	n.281T>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2023

The p.D18E variant (also known as c.54T>A), located in coding exon 1 of the MNDA gene, results from a T to A substitution at nucleotide position 54. The aspartic acid at codon 18 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.4
DANN	Benign	0.92
DEOGEN2	Benign	0.0085	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.041
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.057	T
Polyphen		0.18	B
Vest4		0.070
MutPred		0.69		Loss of loop (P = 0.0986);
MVP		0.57
MPC		0.010
ClinPred		0.13	T
GERP RS		0.83
Varity_R		0.15
gMVP		0.023

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

Other links and lift over

dbSNP: rs1558056521; hg19: chr1-158811997;