NM_001256378.2:c.1114A>C

Variant names:

• chr10-119842482-T-G
• rs1852467157
• NM_001256378.2:c.1114A>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001256378.2(MCMBP):​c.1114A>C​(p.Ile372Leu) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00027 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MCMBP NM_001256378.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.83
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.38360545).

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.1114A>C	p.Ile372Leu	missense	Exon 10 of 16	NP_001243307.1	A0A0S2Z5P5
	MCMBP	NM_024834.4		c.1120A>C	p.Ile374Leu	missense	Exon 10 of 16	NP_079110.1	Q9BTE3-1
	MCMBP	NM_001256379.2		c.595A>C	p.Ile199Leu	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.1114A>C	p.Ile372Leu	missense	Exon 10 of 16	ENSP00000358073.3	Q9BTE3-2
	MCMBP	ENST00000360003.7	TSL:2	c.1120A>C	p.Ile374Leu	missense	Exon 10 of 16	ENSP00000353098.3	Q9BTE3-1
	MCMBP	ENST00000966480.1		c.1120A>C	p.Ile374Leu	missense	Exon 10 of 16	ENSP00000636539.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151958 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000946

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000275 AC: 399 AN: 1452150 Hom.: 0 Cov.: 31 AF XY: 0.000235 AC XY: 170 AN XY: 722740

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000301 AC: 10 AN: 33252

American (AMR) AF: 0.0000673 AC: 3 AN: 44568

Ashkenazi Jewish (ASJ) AF: 0.000192 AC: 5 AN: 25994

East Asian (EAS) AF: 0.000152 AC: 6 AN: 39470

South Asian (SAS) AF: 0.000128 AC: 11 AN: 85996

European-Finnish (FIN) AF: 0.000263 AC: 14 AN: 53168

Middle Eastern (MID) AF: 0.000349 AC: 2 AN: 5736

European-Non Finnish (NFE) AF: 0.000300 AC: 331 AN: 1104014

Other (OTH) AF: 0.000284 AC: 17 AN: 59952

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000263 AC: 4 AN: 152076 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74340

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000241 AC: 1 AN: 41486

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.0000946 AC: 1 AN: 10566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67976

Other (OTH) AF: 0.00 AC: 0 AN: 2110

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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	Benign	0.11
PhyloP100		4.8
Varity_R		0.17
gMVP		0.60
Mutation Taster		=57/43	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

dbSNP: rs1852467157; hg19: chr10-121601994;