10-13164233-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.549

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]

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	UniProt
MCM10	NM_018518.5	c.7+24A>T		intron_variant		ENST00000378714.8
MCM10	NM_182751.3	c.7+24A>T		intron_variant
MCM10	XM_011519538.3	c.7+24A>T		intron_variant
MCM10	XM_047425437.1	c.7+24A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCM10	ENST00000378714.8	c.7+24A>T		intron_variant		1	NM_018518.5	P4
MCM10	ENST00000484800.6	c.7+24A>T		intron_variant		1		A1
MCM10	ENST00000378694.1	c.7+24A>T		intron_variant		5
MCM10	ENST00000479669.5	c.-234+2627A>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.763 AC: 116062 AN: 152026 Hom.: 44515 Cov.: 33

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

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.: 30 AF XY: 0.773 AC XY: 551125 AN XY: 713180

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.: 33 AF XY: 0.766 AC XY: 57012 AN XY: 74390

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

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

Other links and lift over

dbSNP: rs7090944; hg19: chr10-13206233; COSMIC: COSV104430076; COSMIC: COSV104430076;