rs17152897

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018518.5(MCM10):c.401A>G(p.Lys134Arg) variant causes a missense change. The variant allele was found at a frequency of 0.054 in 1,613,844 control chromosomes in the GnomAD database, including 2,708 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.042 ( 186 hom., cov: 32)

Exomes 𝑓: 0.055 ( 2522 hom. )

Consequence

MCM10
NM_018518.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.57

Publications

16 publications found

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 Gene-Disease associations (from GenCC):

immunodeficiency 80 with or without congenital cardiomyopathy
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

MCM10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015130937).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCM10	NM_018518.5 link	c.401A>G	p.Lys134Arg	missense_variant	Exon 4 of 20	ENST00000378714.8	NP_060988.3	Q7L590-2
MCM10	NM_182751.3 link	c.401A>G	p.Lys134Arg	missense_variant	Exon 4 of 20		NP_877428.1	Q7L590-1
MCM10	XM_011519538.3 link	c.401A>G	p.Lys134Arg	missense_variant	Exon 4 of 20		XP_011517840.1	Q7L590-1
MCM10	XM_047425437.1 link	c.401A>G	p.Lys134Arg	missense_variant	Exon 4 of 20		XP_047281393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MCM10	ENST00000378714.8 link	c.401A>G	p.Lys134Arg	missense_variant	Exon 4 of 20	1	NM_018518.5	ENSP00000367986.3	Q7L590-2
MCM10	ENST00000484800.6 link	c.401A>G	p.Lys134Arg	missense_variant	Exon 4 of 20	1		ENSP00000418268.1	Q7L590-1
MCM10	ENST00000378694.1 link	c.401A>G	p.Lys134Arg	missense_variant	Exon 3 of 18	5		ENSP00000367966.1	Q5T670
MCM10	ENST00000479669.5 link	c.161A>G	p.Lys54Arg	missense_variant	Exon 3 of 3	4		ENSP00000417094.1	C9J600

Frequencies

GnomAD3 genomes

AF:

0.0424

AC:

6447

AN:

152188

Hom.:

186

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0105

Gnomad AMI

AF:

0.0636

Gnomad AMR

AF:

0.0759

Gnomad ASJ

AF:

0.0594

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.0671

Gnomad FIN

AF:

0.0368

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0551

Gnomad OTH

AF:

0.0469

GnomAD2 exomes

AF:

0.0563

AC:

14124

AN:

250788

AF XY:

0.0573

show subpopulations

Gnomad AFR exome

AF:

0.00988

Gnomad AMR exome

AF:

0.108

Gnomad ASJ exome

AF:

0.0670

Gnomad EAS exome

AF:

0.00201

Gnomad FIN exome

AF:

0.0358

Gnomad NFE exome

AF:

0.0536

Gnomad OTH exome

AF:

0.0646

GnomAD4 exome

AF:

0.0552

AC:

80631

AN:

1461536

Hom.:

2522

Cov.:

AF XY:

0.0558

AC XY:

40575

AN XY:

727094

show subpopulations

African (AFR)

AF:

0.00848

AC:

284

AN:

33478

American (AMR)

AF:

0.105

AC:

4695

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.0672

AC:

1755

AN:

26130

East Asian (EAS)

AF:

0.00141

AC:

AN:

39700

South Asian (SAS)

AF:

0.0761

AC:

6559

AN:

86240

European-Finnish (FIN)

AF:

0.0376

AC:

2009

AN:

53402

Middle Eastern (MID)

AF:

0.0576

AC:

332

AN:

5768

European-Non Finnish (NFE)

AF:

0.0555

AC:

61650

AN:

1111736

Other (OTH)

AF:

0.0545

AC:

3291

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

3594

7188

10783

14377

17971

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2294

4588

6882

9176

11470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0424

AC:

6456

AN:

152308

Hom.:

186

Cov.:

AF XY:

0.0421

AC XY:

3135

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0105

AC:

436

AN:

41572

American (AMR)

AF:

0.0763

AC:

1167

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0594

AC:

206

AN:

3470

East Asian (EAS)

AF:

0.00212

AC:

AN:

5186

South Asian (SAS)

AF:

0.0674

AC:

325

AN:

4824

European-Finnish (FIN)

AF:

0.0368

AC:

390

AN:

10612

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0551

AC:

3751

AN:

68036

Other (OTH)

AF:

0.0478

AC:

101

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

303

606

908

1211

1514

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0519

Hom.:

473

Bravo

AF:

0.0454

TwinsUK

AF:

0.0583

AC:

216

ALSPAC

AF:

0.0527

AC:

203

ESP6500AA

AF:

0.0116

AC:

ESP6500EA

AF:

0.0594

AC:

511

ExAC

AF:

0.0534

AC:

6483

Asia WGS

AF:

0.0400

AC:

140

AN:

3478

EpiCase

AF:

0.0561

EpiControl

AF:

0.0525

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.046

.;T;T;.

Eigen

Benign

-0.054

Eigen_PC

Benign

-0.028

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.87

D;D;D;D

MetaRNN

Benign

0.0015

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;.;M;.

PhyloP100

4.6

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.1

N;N;N;N

REVEL

Benign

0.15

Sift

Benign

0.032

D;T;D;D

Sift4G

Benign

0.082

T;D;T;T

Polyphen

0.51

P;.;B;P

Vest4

0.040

MPC

0.084

ClinPred

0.029

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.086

Mutation Taster

=89/11

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over