Variant 10-13171148-TG-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_018518.5(MCM10):c.236del(p.Gly79GlufsTer6) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

MCM10
NM_018518.5 frameshift

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 7.81

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 10-13171148-TG-T is Pathogenic according to our data. Variant chr10-13171148-TG-T is described in ClinVar as [Pathogenic]. Clinvar id is 1077166.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MCM10	NM_018518.5 linkuse as main transcript	c.236del	p.Gly79GlufsTer6	frameshift_variant	3/20	ENST00000378714.8	NP_060988.3
MCM10	NM_182751.3 linkuse as main transcript	c.236del	p.Gly79GlufsTer6	frameshift_variant	3/20		NP_877428.1
MCM10	XM_011519538.3 linkuse as main transcript	c.236del	p.Gly79GlufsTer6	frameshift_variant	3/20		XP_011517840.1
MCM10	XM_047425437.1 linkuse as main transcript	c.236del	p.Gly79GlufsTer6	frameshift_variant	3/20		XP_047281393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCM10	ENST00000378714.8 linkuse as main transcript	c.236del	p.Gly79GlufsTer6	frameshift_variant	3/20	1	NM_018518.5	ENSP00000367986	P4	Q7L590-2
MCM10	ENST00000484800.6 linkuse as main transcript	c.236del	p.Gly79GlufsTer6	frameshift_variant	3/20	1		ENSP00000418268	A1	Q7L590-1
MCM10	ENST00000378694.1 linkuse as main transcript	c.236del	p.Gly79GlufsTer6	frameshift_variant	2/18	5		ENSP00000367966
MCM10	ENST00000479669.5 linkuse as main transcript	c.-5del		5_prime_UTR_variant	2/3	4		ENSP00000417094

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000225

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Immunodeficiency 80 with or without congenital cardiomyopathy

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 11, 2021

- -

Fetal Cardiomyopathy

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust

Mar 23, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over