10-13171022-T-C

Position:

• chr10-13171022-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_018518.5(MCM10):​c.108T>C​(p.Asn36=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00165 in 1,614,158 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (8 hom.)
• Consequence: MCM10 NM_018518.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.04

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 10-13171022-T-C is Benign according to our data. Variant chr10-13171022-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2640309.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.04 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCM10	NM_018518.5	c.108T>C	p.Asn36=	synonymous_variant	3/20	ENST00000378714.8	NP_060988.3
MCM10	NM_182751.3	c.108T>C	p.Asn36=	synonymous_variant	3/20		NP_877428.1
MCM10	XM_011519538.3	c.108T>C	p.Asn36=	synonymous_variant	3/20		XP_011517840.1
MCM10	XM_047425437.1	c.108T>C	p.Asn36=	synonymous_variant	3/20		XP_047281393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCM10	ENST00000378714.8	c.108T>C	p.Asn36=	synonymous_variant	3/20	1	NM_018518.5	ENSP00000367986	P4
MCM10	ENST00000484800.6	c.108T>C	p.Asn36=	synonymous_variant	3/20	1		ENSP00000418268	A1
MCM10	ENST00000378694.1	c.108T>C	p.Asn36=	synonymous_variant	2/18	5		ENSP00000367966
MCM10	ENST00000479669.5	c.-133T>C		5_prime_UTR_variant	2/3	4		ENSP00000417094

Frequencies

GnomAD3 genomes AF: 0.00150 AC: 228 AN: 152146 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00253

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.00152 AC: 381 AN: 251470 Hom.: 2 AF XY: 0.00141 AC XY: 192 AN XY: 135908

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00434

Gnomad NFE exome AF: 0.00234

Gnomad OTH exome AF: 0.00195

GnomAD4 exome AF: 0.00166 AC: 2434 AN: 1461894 Hom.: 8 Cov.: 32 AF XY: 0.00168 AC XY: 1223 AN XY: 727248

Gnomad4 AFR exome AF: 0.000209

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.000497

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00446

Gnomad4 NFE exome AF: 0.00188

Gnomad4 OTH exome AF: 0.00119

GnomAD4 genome AF: 0.00150 AC: 228 AN: 152264 Hom.: 1 Cov.: 32 AF XY: 0.00145 AC XY: 108 AN XY: 74452

Gnomad4 AFR AF: 0.000168

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00377

Gnomad4 NFE AF: 0.00253

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00220 Hom.: 0

Bravo AF: 0.00104

EpiCase AF: 0.00245

EpiControl AF: 0.00178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

MCM10: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.46
DANN	Benign	0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs137855341; hg19: chr10-13213022;