NM_018518.5:c.8-38C>T

Variant names:

• chr10-13170884-C-T
• rs2147279
• NM_018518.5:c.8-38C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• immunodeficiency 80 with or without congenital cardiomyopathy

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018518.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCM10	NM_018518.5	MANE Select	c.8-38C>T		intron	N/A	NP_060988.3
	MCM10	NM_182751.3		c.8-38C>T		intron	N/A	NP_877428.1	Q7L590-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCM10	ENST00000378714.8	TSL:1 MANE Select	c.8-38C>T		intron	N/A	ENSP00000367986.3	Q7L590-2
	MCM10	ENST00000484800.6	TSL:1	c.8-38C>T		intron	N/A	ENSP00000418268.1	Q7L590-1
	MCM10	ENST00000921435.1		c.8-38C>T		intron	N/A	ENSP00000591494.1

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

GnomAD2 exomes AF: 0.729 AC: 169652 AN: 232844 AF XY: 0.738

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 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

African (AFR) AF: 0.779 AC: 24744 AN: 31760

American (AMR) AF: 0.497 AC: 20367 AN: 40994

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 18345 AN: 24612

East Asian (EAS) AF: 0.575 AC: 22564 AN: 39226

South Asian (SAS) AF: 0.735 AC: 60796 AN: 82734

European-Finnish (FIN) AF: 0.774 AC: 40747 AN: 52656

Middle Eastern (MID) AF: 0.708 AC: 3949 AN: 5580

European-Non Finnish (NFE) AF: 0.820 AC: 877629 AN: 1070908

Other (OTH) AF: 0.778 AC: 45242 AN: 58150

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

African (AFR) AF: 0.781 AC: 32399 AN: 41510

American (AMR) AF: 0.618 AC: 9436 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 2571 AN: 3472

East Asian (EAS) AF: 0.571 AC: 2956 AN: 5176

South Asian (SAS) AF: 0.728 AC: 3512 AN: 4826

European-Finnish (FIN) AF: 0.776 AC: 8202 AN: 10576

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.807 AC: 54866 AN: 68006

Other (OTH) AF: 0.745 AC: 1572 AN: 2110

Alfa AF: 0.789 Hom.: 192766

Bravo AF: 0.751

Asia WGS AF: 0.676 AC: 2353 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.017
DANN	Benign	0.34
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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