rs2274109

Positions:

• chr10-13197489-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCM10	NM_018518.5	c.1975-134T>C		intron_variant		ENST00000378714.8	NP_060988.3
MCM10	NM_182751.3	c.1978-134T>C		intron_variant			NP_877428.1
MCM10	XM_011519538.3	c.1978-134T>C		intron_variant			XP_011517840.1
MCM10	XM_047425437.1	c.1975-134T>C		intron_variant			XP_047281393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCM10	ENST00000378714.8	c.1975-134T>C		intron_variant		1	NM_018518.5	ENSP00000367986.3
MCM10	ENST00000484800.6	c.1978-134T>C		intron_variant		1		ENSP00000418268.1
MCM10	ENST00000378694.1	c.1975-134T>C		intron_variant		5		ENSP00000367966.1
MCM10	ENST00000481292.1	n.185-134T>C		intron_variant		2

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

Gnomad4 AFR exome AF: 0.0697

Gnomad4 AMR exome AF: 0.135

Gnomad4 ASJ exome AF: 0.208

Gnomad4 EAS exome AF: 0.0688

Gnomad4 SAS exome AF: 0.187

Gnomad4 FIN exome AF: 0.138

Gnomad4 NFE exome AF: 0.196

Gnomad4 OTH exome AF: 0.177

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

Gnomad4 AFR AF: 0.0710

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.0827

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.177

Alfa AF: 0.174 Hom.: 502

Bravo AF: 0.147

Asia WGS AF: 0.122 AC: 427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.9
DANN	Benign	0.65

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: rs2274109; hg19: chr10-13239489;