NM_001256378.2:c.1602G>C

Variant names:

• chr10-119835645-C-G
• NM_001256378.2:c.1602G>C

Variant summary

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

The NM_001256378.2(MCMBP):​c.1602G>C​(p.Met534Ile) 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. M534T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MCMBP NM_001256378.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.24
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11626482).

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.1602G>C	p.Met534Ile	missense	Exon 14 of 16	NP_001243307.1	A0A0S2Z5P5
	MCMBP	NM_024834.4		c.1608G>C	p.Met536Ile	missense	Exon 14 of 16	NP_079110.1	Q9BTE3-1
	MCMBP	NM_001256379.2		c.1083G>C	p.Met361Ile	missense	Exon 14 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.1602G>C	p.Met534Ile	missense	Exon 14 of 16	ENSP00000358073.3	Q9BTE3-2
	MCMBP	ENST00000360003.7	TSL:2	c.1608G>C	p.Met536Ile	missense	Exon 14 of 16	ENSP00000353098.3	Q9BTE3-1
	MCMBP	ENST00000966480.1		c.1608G>C	p.Met536Ile	missense	Exon 14 of 16	ENSP00000636539.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	Uncertain	0.38
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		2.2
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.097
Sift	Benign	0.62	T
Sift4G	Benign	0.21	T
Polyphen		0.0010	B
Vest4		0.46
MutPred		0.45		Loss of disorder (P = 0.0781)
MVP		0.068
MPC		0.31
ClinPred		0.37	T
GERP RS		4.6
Varity_R		0.12
gMVP		0.45
Mutation Taster		=96/4	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: chr10-121595157;