10-119835614-C-A

Variant names:

• chr10-119835614-C-A
• rs769222269
• NM_001256378.2:c.1633G>T

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.1633G>T​(p.Val545Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V545M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: MCMBP NM_001256378.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35
• 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=0.20078969).

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.1633G>T	p.Val545Leu	missense	Exon 14 of 16	NP_001243307.1	A0A0S2Z5P5
	MCMBP	NM_024834.4		c.1639G>T	p.Val547Leu	missense	Exon 14 of 16	NP_079110.1	Q9BTE3-1
	MCMBP	NM_001256379.2		c.1114G>T	p.Val372Leu	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.1633G>T	p.Val545Leu	missense	Exon 14 of 16	ENSP00000358073.3	Q9BTE3-2
	MCMBP	ENST00000360003.7	TSL:2	c.1639G>T	p.Val547Leu	missense	Exon 14 of 16	ENSP00000353098.3	Q9BTE3-1
	MCMBP	ENST00000966480.1		c.1639G>T	p.Val547Leu	missense	Exon 14 of 16	ENSP00000636539.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461854 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727232

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111980

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.7
DANN	Benign	0.65
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.40
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.27	N
PhyloP100		1.4
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.38	N
REVEL	Benign	0.041
Sift	Benign	0.46	T
Sift4G	Benign	0.68	T
Polyphen		0.0010	B
Vest4		0.21
MutPred		0.28		Loss of methylation at K550 (P = 0.0763)
MVP		0.043
MPC		0.28
ClinPred		0.12	T
GERP RS		3.4
Varity_R		0.018
gMVP		0.29
Mutation Taster		=95/5	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

dbSNP: rs769222269; hg19: chr10-121595126;