10-13197489-T-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018518.5(MCM10):​c.1975-134T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 535,554 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: MCM10 NM_018518.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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.1975-134T>G		intron	N/A	NP_060988.3
	MCM10	NM_182751.3		c.1978-134T>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.1975-134T>G		intron	N/A	ENSP00000367986.3	Q7L590-2
	MCM10	ENST00000484800.6	TSL:1	c.1978-134T>G		intron	N/A	ENSP00000418268.1	Q7L590-1
	MCM10	ENST00000921435.1		c.1978-134T>G		intron	N/A	ENSP00000591494.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000187 AC: 1 AN: 535554 Hom.: 0 AF XY: 0.00000356 AC XY: 1 AN XY: 280692

African (AFR) AF: 0.00 AC: 0 AN: 13788

American (AMR) AF: 0.00 AC: 0 AN: 17764

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14238

East Asian (EAS) AF: 0.00 AC: 0 AN: 31500

South Asian (SAS) AF: 0.00 AC: 0 AN: 43908

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36582

Middle Eastern (MID) AF: 0.000444 AC: 1 AN: 2254

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 346834

Other (OTH) AF: 0.00 AC: 0 AN: 28686

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.6
DANN	Benign	0.61
PhyloP100		0.0040

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;