Variant 10-13164233-A-T 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.7+24A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.77 in 1,585,578 control chromosomes in the GnomAD database, including 471,722 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.76 ( 44557 hom., cov: 33)

Exomes 𝑓: 0.77 ( 427165 hom. )

Consequence

MCM10
NM_018518.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.549

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=-0.74).

BP6

Variant 10-13164233-A-T is Benign according to our data. Variant chr10-13164233-A-T is described in ClinVar as [Benign]. Clinvar id is 2688292.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
MCM10	NM_018518.5 linkuse as main transcript	c.7+24A>T	intron_variant	ENST00000378714.8	NP_060988.3
MCM10	NM_182751.3 linkuse as main transcript	c.7+24A>T	intron_variant		NP_877428.1
MCM10	XM_011519538.3 linkuse as main transcript	c.7+24A>T	intron_variant		XP_011517840.1
MCM10	XM_047425437.1 linkuse as main transcript	c.7+24A>T	intron_variant		XP_047281393.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
MCM10	ENST00000378714.8 linkuse as main transcript	c.7+24A>T	intron_variant	1	NM_018518.5	ENSP00000367986	P4	Q7L590-2
MCM10	ENST00000484800.6 linkuse as main transcript	c.7+24A>T	intron_variant	1		ENSP00000418268	A1	Q7L590-1
MCM10	ENST00000378694.1 linkuse as main transcript	c.7+24A>T	intron_variant	5		ENSP00000367966
MCM10	ENST00000479669.5 linkuse as main transcript	c.-234+2627A>T	intron_variant	4		ENSP00000417094

Frequencies

GnomAD3 genomes

AF:

0.763

AC:

116062

AN:

152026

Hom.:

44515

Cov.:

show subpopulations

Gnomad AFR

AF:

0.705

Gnomad AMI

AF:

0.868

Gnomad AMR

AF:

0.844

Gnomad ASJ

AF:

0.838

Gnomad EAS

AF:

0.888

Gnomad SAS

AF:

0.828

Gnomad FIN

AF:

0.735

Gnomad MID

AF:

0.921

Gnomad NFE

AF:

0.764

Gnomad OTH

AF:

0.793

GnomAD3 exomes

AF:

0.796

AC:

180771

AN:

227222

Hom.:

72424

AF XY:

0.796

AC XY:

98256

AN XY:

123496

show subpopulations

Gnomad AFR exome

AF:

0.697

Gnomad AMR exome

AF:

0.896

Gnomad ASJ exome

AF:

0.843

Gnomad EAS exome

AF:

0.898

Gnomad SAS exome

AF:

0.823

Gnomad FIN exome

AF:

0.740

Gnomad NFE exome

AF:

0.769

Gnomad OTH exome

AF:

0.808

GnomAD4 exome

AF:

0.771

AC:

1104870

AN:

1433434

Hom.:

427165

Cov.:

AF XY:

0.773

AC XY:

551125

AN XY:

713180

show subpopulations

Gnomad4 AFR exome

AF:

0.696

Gnomad4 AMR exome

AF:

0.890

Gnomad4 ASJ exome

AF:

0.842

Gnomad4 EAS exome

AF:

0.857

Gnomad4 SAS exome

AF:

0.827

Gnomad4 FIN exome

AF:

0.744

Gnomad4 NFE exome

AF:

0.760

Gnomad4 OTH exome

AF:

0.790

GnomAD4 genome

AF:

0.763

AC:

116155

AN:

152144

Hom.:

44557

Cov.:

AF XY:

0.766

AC XY:

57012

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.706

Gnomad4 AMR

AF:

0.845

Gnomad4 ASJ

AF:

0.838

Gnomad4 EAS

AF:

0.888

Gnomad4 SAS

AF:

0.828

Gnomad4 FIN

AF:

0.735

Gnomad4 NFE

AF:

0.764

Gnomad4 OTH

AF:

0.789

Alfa

AF:

0.773

Hom.:

8394

Bravo

AF:

0.772

Asia WGS

AF:

0.832

AC:

2892

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 96% of patients studied by a panel of primary immunodeficiencies. Number of patients: 91. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

3.0

DANN

Benign

0.88

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