Genetic Variant MCMBP:p.Ile372Leu (chr10-119842482-T-G) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. Variant got -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. 12/21 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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.83

Variant links:

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]

MCMBP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCMBP	NM_001256378.2 link	c.1114A>C	p.Ile372Leu	missense_variant	Exon 10 of 16	ENST00000369077.4	NP_001243307.1	Q9BTE3-2A0A0S2Z5P5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MCMBP	ENST00000369077.4 link	c.1114A>C	p.Ile372Leu	missense_variant	Exon 10 of 16	1	NM_001256378.2	ENSP00000358073.3	Q9BTE3-2
MCMBP	ENST00000360003.7 link	c.1120A>C	p.Ile374Leu	missense_variant	Exon 10 of 16	2		ENSP00000353098.3	Q9BTE3-1
MCMBP	ENST00000466047.5 link	n.1216A>C		non_coding_transcript_exon_variant	Exon 10 of 16	2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151958

Hom.:

Cov.:

FAILED QC

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.:

Cov.:

AF XY:

0.000235

AC XY:

170

AN XY:

722740

show subpopulations

Gnomad4 AFR exome

AF:

0.000301

Gnomad4 AMR exome

AF:

0.0000673

Gnomad4 ASJ exome

AF:

0.000192

Gnomad4 EAS exome

AF:

0.000152

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.000263

Gnomad4 NFE exome

AF:

0.000300

Gnomad4 OTH exome

AF:

0.000284

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000263

AC:

AN:

152076

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000946

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 03, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1120A>C (p.I374L) alteration is located in exon 10 (coding exon 10) of the MCMBP gene. This alteration results from a A to C substitution at nucleotide position 1120, causing the isoleucine (I) at amino acid position 374 to be replaced by a leucine (L). 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

Benign

0.11

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.037

T;.

Eigen

Benign

-0.10

Eigen_PC

Benign

0.13

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.38

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.77

N;.

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.43

N;N

REVEL

Benign

0.13

Sift

Benign

0.50

T;T

Sift4G

Benign

0.49

T;T

Polyphen

0.14

B;.

Vest4

0.46

MutPred

0.72

Gain of catalytic residue at I374 (P = 0.0441);.;

MVP

0.20

MPC

0.31

ClinPred

0.46

GERP RS

5.8

Varity_R

0.17

gMVP

0.60

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over