Variant 10-119853190-T-C 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.434A>G(p.Tyr145Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00021 in 1,612,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

MCMBP
NM_001256378.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.19

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=0.2094653).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCMBP	NM_001256378.2 linkuse as main transcript	c.434A>G	p.Tyr145Cys	missense_variant	6/16	ENST00000369077.4	NP_001243307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCMBP	ENST00000369077.4 linkuse as main transcript	c.434A>G	p.Tyr145Cys	missense_variant	6/16	1	NM_001256378.2	ENSP00000358073	P3	Q9BTE3-2
MCMBP	ENST00000360003.7 linkuse as main transcript	c.434A>G	p.Tyr145Cys	missense_variant	6/16	2		ENSP00000353098	A1	Q9BTE3-1
MCMBP	ENST00000495407.1 linkuse as main transcript	n.905A>G		non_coding_transcript_exon_variant	2/5	2
MCMBP	ENST00000466047.5 linkuse as main transcript	n.554-18A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000227

AC:

AN:

250792

Hom.:

AF XY:

0.000148

AC XY:

AN XY:

135520

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000873

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000414

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000206

AC:

301

AN:

1460444

Hom.:

Cov.:

AF XY:

0.000207

AC XY:

150

AN XY:

726342

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000262

Gnomad4 NFE exome

AF:

0.000239

Gnomad4 OTH exome

AF:

0.0000829

GnomAD4 genome

AF:

0.000250

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000390

Hom.:

Bravo

AF:

0.000230

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000296

AC:

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

Nov 18, 2022

The c.434A>G (p.Y145C) alteration is located in exon 6 (coding exon 6) of the MCMBP gene. This alteration results from a A to G substitution at nucleotide position 434, causing the tyrosine (Y) at amino acid position 145 to be replaced by a cysteine (C). 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

-0.19

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.047

T;.

Eigen

Benign

0.067

Eigen_PC

Benign

0.19

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.0091

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.2

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.22

Sift

Benign

0.060

T;D

Sift4G

Benign

0.070

T;T

Polyphen

0.99

D;.

Vest4

0.56

MVP

0.11

MPC

0.37

ClinPred

0.13

GERP RS

5.0

Varity_R

0.094

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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