NM_001256378.2:c.1114_1116delATCinsTTG

Variant names:

• chr10-119842480-GAT-CAA
• NM_001256378.2:c.1114_1116delATCinsTTG
• MCMBP p.Ile372Leu

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001256378.2(MCMBP):​c.1114_1116delATCinsTTG​(p.Ile372Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MCMBP NM_001256378.2 missense
• Clinical Significance: Not reported in ClinVar
• 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 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.1114_1116delATCinsTTG	p.Ile372Leu	missense	N/A	NP_001243307.1	A0A0S2Z5P5
	MCMBP	NM_024834.4		c.1120_1122delATCinsTTG	p.Ile374Leu	missense	N/A	NP_079110.1	Q9BTE3-1
	MCMBP	NM_001256379.2		c.595_597delATCinsTTG	p.Ile199Leu	missense	N/A	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.1114_1116delATCinsTTG	p.Ile372Leu	missense	N/A	ENSP00000358073.3	Q9BTE3-2
	MCMBP	ENST00000360003.7	TSL:2	c.1120_1122delATCinsTTG	p.Ile374Leu	missense	N/A	ENSP00000353098.3	Q9BTE3-1
	MCMBP	ENST00000966480.1		c.1120_1122delATCinsTTG	p.Ile374Leu	missense	N/A	ENSP00000636539.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-121601992;