rs2274109

Variant names:

• chr10-13197489-T-C
• rs2274109
• NM_018518.5:c.1975-134T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-13197489-T-C
• chr10-13197489-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018518.5(MCM10):​c.1975-134T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 687,146 control chromosomes in the GnomAD database, including 11,161 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (1994 hom., cov: 33)
  • Exomes 𝑓: 0.18 (9167 hom.)
• Consequence: MCM10 NM_018518.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• Publications: 1 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: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.191 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCM10	NM_018518.5	MANE Select	c.1975-134T>C		intron	N/A	NP_060988.3
	MCM10	NM_182751.3		c.1978-134T>C		intron	N/A	NP_877428.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCM10	ENST00000378714.8	TSL:1 MANE Select	c.1975-134T>C		intron	N/A	ENSP00000367986.3
	MCM10	ENST00000484800.6	TSL:1	c.1978-134T>C		intron	N/A	ENSP00000418268.1
	MCM10	ENST00000378694.1	TSL:5	c.1975-134T>C		intron	N/A	ENSP00000367966.1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22650 AN: 152114 Hom.: 1997 Cov.: 33

Gnomad AFR AF: 0.0712

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.0825

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.179

GnomAD4 exome AF: 0.178 AC: 95068 AN: 534914 Hom.: 9167 AF XY: 0.178 AC XY: 49952 AN XY: 280390

African (AFR) AF: 0.0697 AC: 961 AN: 13782

American (AMR) AF: 0.135 AC: 2388 AN: 17750

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 2962 AN: 14224

East Asian (EAS) AF: 0.0688 AC: 2167 AN: 31490

South Asian (SAS) AF: 0.187 AC: 8203 AN: 43872

European-Finnish (FIN) AF: 0.138 AC: 5033 AN: 36548

Middle Eastern (MID) AF: 0.204 AC: 459 AN: 2252

European-Non Finnish (NFE) AF: 0.196 AC: 67811 AN: 346338

Other (OTH) AF: 0.177 AC: 5084 AN: 28658

GnomAD4 genome AF: 0.149 AC: 22636 AN: 152232 Hom.: 1994 Cov.: 33 AF XY: 0.146 AC XY: 10860 AN XY: 74428

African (AFR) AF: 0.0710 AC: 2950 AN: 41532

American (AMR) AF: 0.155 AC: 2375 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 707 AN: 3472

East Asian (EAS) AF: 0.0827 AC: 429 AN: 5190

South Asian (SAS) AF: 0.195 AC: 943 AN: 4834

European-Finnish (FIN) AF: 0.134 AC: 1416 AN: 10594

Middle Eastern (MID) AF: 0.175 AC: 51 AN: 292

European-Non Finnish (NFE) AF: 0.194 AC: 13190 AN: 67996

Other (OTH) AF: 0.177 AC: 374 AN: 2114

Alfa AF: 0.175 Hom.: 877

Bravo AF: 0.147

Asia WGS AF: 0.122 AC: 427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.9
DANN	Benign	0.65
PhyloP100		0.0040
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: rs2274109; hg19: chr10-13239489;