10-13172812-A-G

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.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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.87

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=-0.91).
• 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	HGVSp	Effect	#exon/exons	MANE	UniProt
MCM10	NM_018518.5	c.592+47A>G		intron_variant		ENST00000378714.8
MCM10	NM_182751.3	c.595+47A>G		intron_variant
MCM10	XM_011519538.3	c.595+47A>G		intron_variant
MCM10	XM_047425437.1	c.592+47A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCM10	ENST00000378714.8	c.592+47A>G		intron_variant		1	NM_018518.5	P4
MCM10	ENST00000484800.6	c.595+47A>G		intron_variant		1		A1
MCM10	ENST00000378694.1	c.592+47A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.772 AC: 117272 AN: 151832 Hom.: 45606 Cov.: 31

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

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.: 28 AF XY: 0.794 AC XY: 573593 AN XY: 722054

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.: 31 AF XY: 0.766 AC XY: 56874 AN XY: 74272

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

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

Other links and lift over

dbSNP: rs6602637; hg19: chr10-13214812; COSMIC: COSV66334582; COSMIC: COSV66334582;