10-13170884-C-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.8-38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 1,558,772 control chromosomes in the GnomAD database, including 490,402 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.77 (44981 hom., cov: 33)
  • Exomes 𝑓: 0.79 (445421 hom.)
• Consequence: MCM10 NM_018518.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.68

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=-0.97).
• BP6: Variant 10-13170884-C-T is Benign according to our data. Variant chr10-13170884-C-T is described in ClinVar as [Benign]. Clinvar id is 2687950.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCM10	NM_018518.5	c.8-38C>T		intron_variant		ENST00000378714.8
MCM10	NM_182751.3	c.8-38C>T		intron_variant
MCM10	XM_011519538.3	c.8-38C>T		intron_variant
MCM10	XM_047425437.1	c.8-38C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCM10	ENST00000378714.8	c.8-38C>T		intron_variant		1	NM_018518.5	P4
MCM10	ENST00000484800.6	c.8-38C>T		intron_variant		1		A1
MCM10	ENST00000378694.1	c.8-38C>T		intron_variant		5
MCM10	ENST00000479669.5	c.-233-38C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.765 AC: 116311 AN: 152034 Hom.: 44941 Cov.: 33

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.767

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.776

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.745

GnomAD3 exomes AF: 0.729 AC: 169652 AN: 232844 Hom.: 63642 AF XY: 0.738 AC XY: 93547 AN XY: 126824

Gnomad AFR exome AF: 0.786

Gnomad AMR exome AF: 0.476

Gnomad ASJ exome AF: 0.746

Gnomad EAS exome AF: 0.571

Gnomad SAS exome AF: 0.734

Gnomad FIN exome AF: 0.766

Gnomad NFE exome AF: 0.810

Gnomad OTH exome AF: 0.746

GnomAD4 exome AF: 0.792 AC: 1114383 AN: 1406620 Hom.: 445421 Cov.: 22 AF XY: 0.791 AC XY: 553379 AN XY: 699580

Gnomad4 AFR exome AF: 0.779

Gnomad4 AMR exome AF: 0.497

Gnomad4 ASJ exome AF: 0.745

Gnomad4 EAS exome AF: 0.575

Gnomad4 SAS exome AF: 0.735

Gnomad4 FIN exome AF: 0.774

Gnomad4 NFE exome AF: 0.820

Gnomad4 OTH exome AF: 0.778

GnomAD4 genome AF: 0.765 AC: 116398 AN: 152152 Hom.: 44981 Cov.: 33 AF XY: 0.758 AC XY: 56358 AN XY: 74372

Gnomad4 AFR AF: 0.781

Gnomad4 AMR AF: 0.618

Gnomad4 ASJ AF: 0.740

Gnomad4 EAS AF: 0.571

Gnomad4 SAS AF: 0.728

Gnomad4 FIN AF: 0.776

Gnomad4 NFE AF: 0.807

Gnomad4 OTH AF: 0.745

Alfa AF: 0.792 Hom.: 84832

Bravo AF: 0.751

Asia WGS AF: 0.676 AC: 2353 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	-0.97
Cadd	Benign	0.017
Dann	Benign	0.34

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: rs2147279; hg19: chr10-13212884; COSMIC: COSV66333103;