19-4345839-A-C

Variant names:

• chr19-4345839-A-C
• NM_001300862.2:c.389A>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001300862.2(MPND):​c.389A>C​(p.His130Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MPND NM_001300862.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.46
• Publications: 0 publications found

Genes affected

MPND (HGNC:25934): (MPN domain containing) Predicted to enable histone binding activity; peptidase activity; and transcription coactivator activity. Predicted to be involved in chromatin remodeling and positive regulation of transcription by RNA polymerase II. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.765

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300862.2. 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
	MPND	NM_001300862.2	MANE Select	c.389A>C	p.His130Pro	missense	Exon 3 of 13	NP_001287791.1	W4VSR2
	MPND	NM_032868.6		c.389A>C	p.His130Pro	missense	Exon 3 of 12	NP_116257.2
	MPND	NM_001159846.3		c.389A>C	p.His130Pro	missense	Exon 3 of 11	NP_001153318.1	Q8N594-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPND	ENST00000599840.6	TSL:5 MANE Select	c.389A>C	p.His130Pro	missense	Exon 3 of 13	ENSP00000471735.1	W4VSR2
	MPND	ENST00000262966.12	TSL:1	c.389A>C	p.His130Pro	missense	Exon 3 of 12	ENSP00000262966.7	Q8N594-1
	MPND	ENST00000594716.5	TSL:1	n.389A>C		non_coding_transcript_exon	Exon 3 of 12	ENSP00000470987.1	M0R044

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	29
DANN	Uncertain	0.98
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.096	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		8.5
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-8.2	D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.85
MutPred		0.57		Gain of catalytic residue at H130 (P = 0.0021)
MVP		0.75
MPC		1.5
ClinPred		1.0	D
GERP RS		4.2
Varity_R		0.90
gMVP		0.87
Mutation Taster		=21/79	disease causing

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

Other links and lift over

hg19: chr19-4345836;