rs7905784

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.1618A>T(p.Thr540Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,613,626 control chromosomes in the GnomAD database, including 18,506 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.12 ( 1393 hom., cov: 32)

Exomes 𝑓: 0.14 ( 17113 hom. )

Consequence

MCM10
NM_018518.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.54

Publications

21 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=0.0028232634).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCM10	NM_018518.5 link	c.1618A>T	p.Thr540Ser	missense_variant	Exon 12 of 20	ENST00000378714.8	NP_060988.3	Q7L590-2
MCM10	NM_182751.3 link	c.1621A>T	p.Thr541Ser	missense_variant	Exon 12 of 20		NP_877428.1	Q7L590-1
MCM10	XM_011519538.3 link	c.1621A>T	p.Thr541Ser	missense_variant	Exon 12 of 20		XP_011517840.1	Q7L590-1
MCM10	XM_047425437.1 link	c.1618A>T	p.Thr540Ser	missense_variant	Exon 12 of 20		XP_047281393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MCM10	ENST00000378714.8 link	c.1618A>T	p.Thr540Ser	missense_variant	Exon 12 of 20	1	NM_018518.5	ENSP00000367986.3	Q7L590-2
MCM10	ENST00000484800.6 link	c.1621A>T	p.Thr541Ser	missense_variant	Exon 12 of 20	1		ENSP00000418268.1	Q7L590-1
MCM10	ENST00000378694.1 link	c.1618A>T	p.Thr540Ser	missense_variant	Exon 11 of 18	5		ENSP00000367966.1	Q5T670
MCM10	ENST00000459751.1 link	n.-135A>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

18592

AN:

152012

Hom.:

1392

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0833

Gnomad AMI

AF:

0.0570

Gnomad AMR

AF:

0.0679

Gnomad ASJ

AF:

0.0579

Gnomad EAS

AF:

0.0231

Gnomad SAS

AF:

0.0374

Gnomad FIN

AF:

0.223

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.162

Gnomad OTH

AF:

0.0868

GnomAD2 exomes

AF:

0.115

AC:

28832

AN:

251270

AF XY:

0.114

show subpopulations

Gnomad AFR exome

AF:

0.0819

Gnomad AMR exome

AF:

0.0467

Gnomad ASJ exome

AF:

0.0525

Gnomad EAS exome

AF:

0.0264

Gnomad FIN exome

AF:

0.225

Gnomad NFE exome

AF:

0.159

Gnomad OTH exome

AF:

0.113

GnomAD4 exome

AF:

0.144

AC:

210785

AN:

1461496

Hom.:

17113

Cov.:

AF XY:

0.141

AC XY:

102822

AN XY:

727084

show subpopulations

African (AFR)

AF:

0.0798

AC:

2672

AN:

33474

American (AMR)

AF:

0.0493

AC:

2203

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.0521

AC:

1361

AN:

26136

East Asian (EAS)

AF:

0.0225

AC:

895

AN:

39698

South Asian (SAS)

AF:

0.0417

AC:

3594

AN:

86240

European-Finnish (FIN)

AF:

0.220

AC:

11755

AN:

53412

Middle Eastern (MID)

AF:

0.0321

AC:

185

AN:

5768

European-Non Finnish (NFE)

AF:

0.163

AC:

180977

AN:

1111676

Other (OTH)

AF:

0.118

AC:

7143

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

8832

17663

26495

35326

44158

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6212

12424

18636

24848

31060

<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:

0.122

AC:

18610

AN:

152130

Hom.:

1393

Cov.:

AF XY:

0.121

AC XY:

9030

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.0834

AC:

3464

AN:

41514

American (AMR)

AF:

0.0677

AC:

1035

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0579

AC:

201

AN:

3472

East Asian (EAS)

AF:

0.0234

AC:

121

AN:

5180

South Asian (SAS)

AF:

0.0374

AC:

180

AN:

4812

European-Finnish (FIN)

AF:

0.223

AC:

2359

AN:

10574

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.162

AC:

11006

AN:

67982

Other (OTH)

AF:

0.0859

AC:

181

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

830

1660

2489

3319

4149

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

206

412

618

824

1030

<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:

0.144

Hom.:

1377

Bravo

AF:

0.108

TwinsUK

AF:

0.163

AC:

606

ALSPAC

AF:

0.159

AC:

614

ESP6500AA

AF:

0.0881

AC:

388

ESP6500EA

AF:

0.146

AC:

1258

ExAC

AF:

0.118

AC:

14272

Asia WGS

AF:

0.0380

AC:

132

AN:

3478

EpiCase

AF:

0.141

EpiControl

AF:

0.139

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

3.0

(source)

DANN

Benign

0.29

DEOGEN2

Benign

0.030

.;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.35

T;T;T

MetaRNN

Benign

0.0028

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.1

.;L;.

PhyloP100

1.5

PrimateAI

Benign

0.33

PROVEAN

Benign

0.080

N;N;N

REVEL

Benign

0.085

Sift

Benign

0.65

T;T;T

Sift4G

Benign

0.44

T;T;T

Polyphen

0.0020

B;B;B

Vest4

0.020

MPC

0.091

ClinPred

0.0011

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.026

gMVP

0.080

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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