10-13171243-A-G

Variant summary

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

The NM_018518.5(MCM10):c.329A>G(p.Lys110Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,610,558 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 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MCM10
NM_018518.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.66

Variant links:

Genes affected

MCM10 (HGNC:18043): (minichromosome maintenance 10 replication initiation factor) The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are involved in the initiation of eukaryotic genome replication. The hexameric protein complex formed by MCM proteins is a key component of the pre-replication complex (pre-RC) and it may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. This protein can interact with MCM2 and MCM6, as well as with the origin recognition protein ORC2. It is regulated by proteolysis and phosphorylation in a cell cycle-dependent manner. Studies of a similar protein in Xenopus suggest that the chromatin binding of this protein at the onset of DNA replication is after pre-RC assembly and before origin unwinding. Alternatively spliced transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Jul 2008]

MCM10 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=0.18109891).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MCM10	NM_018518.5 linkuse as main transcript	c.329A>G	p.Lys110Arg	missense_variant	3/20	ENST00000378714.8
MCM10	NM_182751.3 linkuse as main transcript	c.329A>G	p.Lys110Arg	missense_variant	3/20
MCM10	XM_011519538.3 linkuse as main transcript	c.329A>G	p.Lys110Arg	missense_variant	3/20
MCM10	XM_047425437.1 linkuse as main transcript	c.329A>G	p.Lys110Arg	missense_variant	3/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCM10	ENST00000378714.8 linkuse as main transcript	c.329A>G	p.Lys110Arg	missense_variant	3/20	1	NM_018518.5	P4	Q7L590-2
MCM10	ENST00000484800.6 linkuse as main transcript	c.329A>G	p.Lys110Arg	missense_variant	3/20	1		A1	Q7L590-1
MCM10	ENST00000378694.1 linkuse as main transcript	c.329A>G	p.Lys110Arg	missense_variant	2/18	5
MCM10	ENST00000479669.5 linkuse as main transcript	c.89A>G	p.Lys30Arg	missense_variant	2/3	4

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458310

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725328

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000660

Hom.:

EpiCase

AF:

0.0000545

EpiControl

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2023

The c.329A>G (p.K110R) alteration is located in exon 3 (coding exon 2) of the MCM10 gene. This alteration results from a A to G substitution at nucleotide position 329, causing the lysine (K) at amino acid position 110 to be replaced by an arginine (R). 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

-0.51

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.81

T;T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.18

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

M;.;M;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.2

N;D;N;N

REVEL

Benign

0.16

Sift

Benign

0.11

T;D;T;T

Sift4G

Uncertain

0.029

D;D;D;D

Polyphen

1.0

D;.;D;D

Vest4

0.31

MutPred

0.089

Loss of ubiquitination at K110 (P = 0.0012);.;Loss of ubiquitination at K110 (P = 0.0012);Loss of ubiquitination at K110 (P = 0.0012);

MVP

0.27

MPC

0.44

ClinPred

0.93

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.041

gMVP

0.085

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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