10-119842523-A-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.824

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCMBP	NM_001256378.2	c.1073T>C	p.Leu358Pro	missense_variant	Exon 10 of 16	ENST00000369077.4	NP_001243307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCMBP	ENST00000369077.4	c.1073T>C	p.Leu358Pro	missense_variant	Exon 10 of 16	1	NM_001256378.2	ENSP00000358073.3
MCMBP	ENST00000360003.7	c.1079T>C	p.Leu360Pro	missense_variant	Exon 10 of 16	2		ENSP00000353098.3
MCMBP	ENST00000466047.5	n.1175T>C		non_coding_transcript_exon_variant	Exon 10 of 16	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 06, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1079T>C (p.L360P) alteration is located in exon 10 (coding exon 10) of the MCMBP gene. This alteration results from a T to C substitution at nucleotide position 1079, causing the leucine (L) at amino acid position 360 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;D
M_CAP	Benign	0.041	D
MetaRNN	Pathogenic	0.82	D;D
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-4.1	D;D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.030	D;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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-121602035;