Variant 10-119853181-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001256378.2(MCMBP):c.443C>T(p.Ala148Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000744 in 1,613,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

MCMBP
NM_001256378.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.70

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13790855).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCMBP	NM_001256378.2 linkuse as main transcript	c.443C>T	p.Ala148Val	missense_variant	6/16	ENST00000369077.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCMBP	ENST00000369077.4 linkuse as main transcript	c.443C>T	p.Ala148Val	missense_variant	6/16	1	NM_001256378.2	P3	Q9BTE3-2
MCMBP	ENST00000360003.7 linkuse as main transcript	c.443C>T	p.Ala148Val	missense_variant	6/16	2		A1	Q9BTE3-1
MCMBP	ENST00000495407.1 linkuse as main transcript	n.914C>T		non_coding_transcript_exon_variant	2/5	2
MCMBP	ENST00000466047.5 linkuse as main transcript	n.554-9C>T		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461362

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726960

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 20, 2023

The c.443C>T (p.A148V) alteration is located in exon 6 (coding exon 6) of the MCMBP gene. This alteration results from a C to T substitution at nucleotide position 443, causing the alanine (A) at amino acid position 148 to be replaced by a valine (V). 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

0.087

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Benign

-0.32

Cadd

Uncertain

Dann

Uncertain

0.98

DEOGEN2

Benign

0.018

T;.

Eigen

Benign

0.0040

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.0013

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.0

L;L

MutationTaster

Benign

0.63

D;D

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.35

N;N

REVEL

Benign

0.23

Sift

Benign

0.24

T;T

Sift4G

Benign

0.49

T;T

Polyphen

0.0020

B;.

Vest4

0.35

MutPred

0.40

Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);

MVP

0.082

MPC

0.40

ClinPred

0.29

GERP RS

6.2

Varity_R

0.067

gMVP

0.20

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

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