rs6602637

Variant names:

• chr10-13172812-A-G
• rs6602637
• NM_018518.5:c.592+47A>G

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.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
• Publications: 5 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=-0.91).
• BP6: Variant 10-13172812-A-G is Benign according to our data. Variant chr10-13172812-A-G is described in ClinVar as Benign. ClinVar VariationId 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.

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.592+47A>G		intron	N/A	NP_060988.3
	MCM10	NM_182751.3		c.595+47A>G		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.592+47A>G		intron	N/A	ENSP00000367986.3	Q7L590-2
	MCM10	ENST00000484800.6	TSL:1	c.595+47A>G		intron	N/A	ENSP00000418268.1	Q7L590-1
	MCM10	ENST00000921435.1		c.595+47A>G		intron	N/A	ENSP00000591494.1

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

GnomAD2 exomes AF: 0.741 AC: 182881 AN: 246848 AF XY: 0.747

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 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

African (AFR) AF: 0.783 AC: 26081 AN: 33290

American (AMR) AF: 0.573 AC: 25380 AN: 44308

Ashkenazi Jewish (ASJ) AF: 0.746 AC: 19238 AN: 25782

East Asian (EAS) AF: 0.578 AC: 22926 AN: 39632

South Asian (SAS) AF: 0.737 AC: 62907 AN: 85392

European-Finnish (FIN) AF: 0.774 AC: 41136 AN: 53128

Middle Eastern (MID) AF: 0.710 AC: 3478 AN: 4896

European-Non Finnish (NFE) AF: 0.821 AC: 907065 AN: 1104904

Other (OTH) AF: 0.783 AC: 46922 AN: 59958

GnomAD4 genome AF: 0.772 AC: 117367 AN: 151950 Hom.: 45648 Cov.: 31 AF XY: 0.766 AC XY: 56874 AN XY: 74272

African (AFR) AF: 0.787 AC: 32575 AN: 41402

American (AMR) AF: 0.664 AC: 10128 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 2569 AN: 3470

East Asian (EAS) AF: 0.574 AC: 2957 AN: 5148

South Asian (SAS) AF: 0.731 AC: 3514 AN: 4810

European-Finnish (FIN) AF: 0.775 AC: 8183 AN: 10562

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

European-Non Finnish (NFE) AF: 0.808 AC: 54963 AN: 67988

Other (OTH) AF: 0.754 AC: 1590 AN: 2110

Alfa AF: 0.797 Hom.: 27096

Bravo AF: 0.762

Asia WGS AF: 0.683 AC: 2378 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	-0.91
CADD	Benign	0.29
DANN	Benign	0.31
PhyloP100		-2.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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