1-158842183-G-T

Position:

• chr1-158842183-G-T

Variant summary

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

The NM_002432.3(MNDA):​c.30G>T​(p.Leu10Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. L10S) 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: -1.56

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MNDA	NM_002432.3	c.30G>T	p.Leu10Phe	missense_variant	2/7	ENST00000368141.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MNDA	ENST00000368141.5	c.30G>T	p.Leu10Phe	missense_variant	2/7	1	NM_002432.3	P1
MNDA	ENST00000491210.1	n.257G>T		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

Jul 11, 2022

The p.L10F variant (also known as c.30G>T), located in coding exon 1 of the MNDA gene, results from a G to T substitution at nucleotide position 30. The leucine at codon 10 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. 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	0.32
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	6.5
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.016	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.074	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.44
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.37
MutPred		0.80		Loss of ubiquitination at K6 (P = 0.0787);
MVP		0.66
MPC		0.054
ClinPred		0.55	D
GERP RS		-2.5
Varity_R		0.43
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr1-158811973;