chr10-13171247-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_018518.5(MCM10):c.333G>A(p.Thr111Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000776 in 1,609,502 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00050 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00080 ( 1 hom. )

Consequence

MCM10
NM_018518.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.76

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 was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 10-13171247-G-A is Benign according to our data. Variant chr10-13171247-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 709266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.76 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCM10	NM_018518.5 link	c.333G>A	p.Thr111Thr	synonymous_variant	Exon 3 of 20	ENST00000378714.8	NP_060988.3	Q7L590-2
MCM10	NM_182751.3 link	c.333G>A	p.Thr111Thr	synonymous_variant	Exon 3 of 20		NP_877428.1	Q7L590-1
MCM10	XM_011519538.3 link	c.333G>A	p.Thr111Thr	synonymous_variant	Exon 3 of 20		XP_011517840.1	Q7L590-1
MCM10	XM_047425437.1 link	c.333G>A	p.Thr111Thr	synonymous_variant	Exon 3 of 20		XP_047281393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MCM10	ENST00000378714.8 link	c.333G>A	p.Thr111Thr	synonymous_variant	Exon 3 of 20	1	NM_018518.5	ENSP00000367986.3	Q7L590-2
MCM10	ENST00000484800.6 link	c.333G>A	p.Thr111Thr	synonymous_variant	Exon 3 of 20	1		ENSP00000418268.1	Q7L590-1
MCM10	ENST00000378694.1 link	c.333G>A	p.Thr111Thr	synonymous_variant	Exon 2 of 18	5		ENSP00000367966.1	Q5T670
MCM10	ENST00000479669.5 link	c.93G>A	p.Thr31Thr	synonymous_variant	Exon 2 of 3	4		ENSP00000417094.1	C9J600

Frequencies

GnomAD3 genomes

AF:

0.000499

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000867

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000414

AC:

102

AN:

246084

AF XY:

0.000405

show subpopulations

Gnomad AFR exome

AF:

0.000188

Gnomad AMR exome

AF:

0.000119

Gnomad ASJ exome

AF:

0.000713

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.000756

Gnomad OTH exome

AF:

0.000337

GnomAD4 exome

AF:

0.000805

AC:

1173

AN:

1457200

Hom.:

Cov.:

AF XY:

0.000758

AC XY:

549

AN XY:

724668

show subpopulations

Gnomad4 AFR exome

AF:

0.000272

AC:

AN:

33054

Gnomad4 AMR exome

AF:

0.0000916

AC:

AN:

43686

Gnomad4 ASJ exome

AF:

0.000655

AC:

AN:

25974

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39630

Gnomad4 SAS exome

AF:

0.0000117

AC:

AN:

85808

Gnomad4 FIN exome

AF:

0.0000750

AC:

AN:

53346

Gnomad4 NFE exome

AF:

0.000984

AC:

1092

AN:

1109882

Gnomad4 Remaining exome

AF:

0.000765

AC:

AN:

60122

Heterozygous variant carriers

124

186

248

310

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

104

156

208

260

<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:

0.000499

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.000217

AC:

0.000216554

AN:

0.000216554

Gnomad4 AMR

AF:

0.000131

AC:

0.000130685

AN:

0.000130685

Gnomad4 ASJ

AF:

0.00115

AC:

0.00115274

AN:

0.00115274

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.0000943

AC:

0.0000942863

AN:

0.0000942863

Gnomad4 NFE

AF:

0.000867

AC:

0.000867392

AN:

0.000867392

Gnomad4 OTH

AF:

0.000473

AC:

0.000473037

AN:

0.000473037

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<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:

0.000610

Hom.:

Bravo

AF:

0.000419

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.000830

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

MCM10: BP4, BP7 -

Jul 31, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jun 12, 2023

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.2

DANN

Benign

0.40

Mutation Taster

=100/0

polymorphism

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

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