Variant 10-13172812-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_018518.5(MCM10):c.592+47A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 1,603,240 control chromosomes in the GnomAD database, including 508,712 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.77 ( 45648 hom., cov: 31)

Exomes 𝑓: 0.80 ( 463064 hom. )

Consequence

MCM10
NM_018518.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.87

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 10-13172812-A-G is Benign according to our data. Variant chr10-13172812-A-G is described in ClinVar as [Benign]. Clinvar id is 2687951.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
MCM10	NM_018518.5 linkuse as main transcript	c.592+47A>G	intron_variant	ENST00000378714.8	NP_060988.3	Q7L590-2
MCM10	NM_182751.3 linkuse as main transcript	c.595+47A>G	intron_variant		NP_877428.1	Q7L590-1
MCM10	XM_011519538.3 linkuse as main transcript	c.595+47A>G	intron_variant		XP_011517840.1	Q7L590-1
MCM10	XM_047425437.1 linkuse as main transcript	c.592+47A>G	intron_variant		XP_047281393.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
MCM10	ENST00000378714.8 linkuse as main transcript	c.592+47A>G	intron_variant	1	NM_018518.5	ENSP00000367986.3	Q7L590-2
MCM10	ENST00000484800.6 linkuse as main transcript	c.595+47A>G	intron_variant	1		ENSP00000418268.1	Q7L590-1
MCM10	ENST00000378694.1 linkuse as main transcript	c.592+47A>G	intron_variant	5		ENSP00000367966.1	Q5T670

Frequencies

GnomAD3 genomes

AF:

0.772

AC:

117272

AN:

151832

Hom.:

45606

Cov.:

show subpopulations

Gnomad AFR

AF:

0.787

Gnomad AMI

AF:

0.766

Gnomad AMR

AF:

0.664

Gnomad ASJ

AF:

0.740

Gnomad EAS

AF:

0.575

Gnomad SAS

AF:

0.732

Gnomad FIN

AF:

0.775

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.808

Gnomad OTH

AF:

0.753

GnomAD3 exomes

AF:

0.741

AC:

182881

AN:

246848

Hom.:

69093

AF XY:

0.747

AC XY:

99521

AN XY:

133262

show subpopulations

Gnomad AFR exome

AF:

0.791

Gnomad AMR exome

AF:

0.557

Gnomad ASJ exome

AF:

0.748

Gnomad EAS exome

AF:

0.573

Gnomad SAS exome

AF:

0.736

Gnomad FIN exome

AF:

0.767

Gnomad NFE exome

AF:

0.812

Gnomad OTH exome

AF:

0.758

GnomAD4 exome

AF:

0.796

AC:

1155133

AN:

1451290

Hom.:

463064

Cov.:

AF XY:

0.794

AC XY:

573593

AN XY:

722054

show subpopulations

Gnomad4 AFR exome

AF:

0.783

Gnomad4 AMR exome

AF:

0.573

Gnomad4 ASJ exome

AF:

0.746

Gnomad4 EAS exome

AF:

0.578

Gnomad4 SAS exome

AF:

0.737

Gnomad4 FIN exome

AF:

0.774

Gnomad4 NFE exome

AF:

0.821

Gnomad4 OTH exome

AF:

0.783

GnomAD4 genome

AF:

0.772

AC:

117367

AN:

151950

Hom.:

45648

Cov.:

AF XY:

0.766

AC XY:

56874

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.787

Gnomad4 AMR

AF:

0.664

Gnomad4 ASJ

AF:

0.740

Gnomad4 EAS

AF:

0.574

Gnomad4 SAS

AF:

0.731

Gnomad4 FIN

AF:

0.775

Gnomad4 NFE

AF:

0.808

Gnomad4 OTH

AF:

0.754

Alfa

AF:

0.797

Hom.:

24317

Bravo

AF:

0.762

Asia WGS

AF:

0.683

AC:

2378

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 88% of patients studied by a panel of primary immunodeficiencies. Number of patients: 84. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.29

DANN

Benign

0.31

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

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