NM_001256378.2:c.1073T>C

Variant names:

• chr10-119842523-A-G
• NM_001256378.2:c.1073T>C

Variant summary

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

The NM_001256378.2(MCMBP):​c.1073T>C​(p.Leu358Pro) 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: 32)
• Consequence: MCMBP NM_001256378.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.15
• Publications: 0 publications found

Genes affected

MCMBP (HGNC:25782): (minichromosome maintenance complex binding protein) This gene encodes a protein which is a component of the hexameric minichromosome maintenance (MCM) complex which regulates initiation and elongation of DNA. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

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, 0.824

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256378.2. 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
	MCMBP	NM_001256378.2	MANE Select	c.1073T>C	p.Leu358Pro	missense	Exon 10 of 16	NP_001243307.1	A0A0S2Z5P5
	MCMBP	NM_024834.4		c.1079T>C	p.Leu360Pro	missense	Exon 10 of 16	NP_079110.1	Q9BTE3-1
	MCMBP	NM_001256379.2		c.554T>C	p.Leu185Pro	missense	Exon 10 of 16	NP_001243308.1	Q9BTE3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCMBP	ENST00000369077.4	TSL:1 MANE Select	c.1073T>C	p.Leu358Pro	missense	Exon 10 of 16	ENSP00000358073.3	Q9BTE3-2
	MCMBP	ENST00000360003.7	TSL:2	c.1079T>C	p.Leu360Pro	missense	Exon 10 of 16	ENSP00000353098.3	Q9BTE3-1
	MCMBP	ENST00000966480.1		c.1079T>C	p.Leu360Pro	missense	Exon 10 of 16	ENSP00000636539.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.37	T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.041	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		9.2
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.030	D
Polyphen		1.0	D
Vest4		0.89
MutPred		0.67		Gain of loop (P = 0.0111)
MVP		0.47
MPC		1.3
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.83
gMVP		0.88
Mutation Taster		=38/62	disease causing

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

Other links and lift over

hg19: chr10-121602035;