NM_001300862.2:c.496C>T

Variant names:

• chr19-4345946-C-T
• NM_001300862.2:c.496C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001300862.2(MPND):​c.496C>T​(p.His166Tyr) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MPND NM_001300862.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.72
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10569686).

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.496C>T	p.His166Tyr	missense	Exon 3 of 13	NP_001287791.1	W4VSR2
	MPND	NM_032868.6		c.496C>T	p.His166Tyr	missense	Exon 3 of 12	NP_116257.2
	MPND	NM_001159846.3		c.496C>T	p.His166Tyr	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.496C>T	p.His166Tyr	missense	Exon 3 of 13	ENSP00000471735.1	W4VSR2
	MPND	ENST00000262966.12	TSL:1	c.496C>T	p.His166Tyr	missense	Exon 3 of 12	ENSP00000262966.7	Q8N594-1
	MPND	ENST00000594716.5	TSL:1	n.496C>T		non_coding_transcript_exon	Exon 3 of 12	ENSP00000470987.1	M0R044

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	Benign	0.14
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Benign	0.50
DEOGEN2	Benign	0.0086	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.5	L
PhyloP100		2.7
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.057
Sift	Benign	0.60	T
Sift4G	Benign	0.24	T
Polyphen		0.0080	B
Vest4		0.27
MutPred		0.30		Loss of disorder (P = 0.0615)
MVP		0.43
MPC		0.49
ClinPred		0.16	T
GERP RS		3.2
Varity_R		0.045
gMVP		0.26
Mutation Taster		=78/22	polymorphism

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: chr19-4345943;