chr10-13192356-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018518.5(MCM10):​c.1618A>T​(p.Thr540Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,613,626 control chromosomes in the GnomAD database, including 18,506 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 1393 hom., cov: 32)
Exomes 𝑓: 0.14 ( 17113 hom. )

Consequence

MCM10
NM_018518.5 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.54
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0028232634).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MCM10NM_018518.5 linkuse as main transcriptc.1618A>T p.Thr540Ser missense_variant 12/20 ENST00000378714.8 NP_060988.3
MCM10NM_182751.3 linkuse as main transcriptc.1621A>T p.Thr541Ser missense_variant 12/20 NP_877428.1
MCM10XM_011519538.3 linkuse as main transcriptc.1621A>T p.Thr541Ser missense_variant 12/20 XP_011517840.1
MCM10XM_047425437.1 linkuse as main transcriptc.1618A>T p.Thr540Ser missense_variant 12/20 XP_047281393.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MCM10ENST00000378714.8 linkuse as main transcriptc.1618A>T p.Thr540Ser missense_variant 12/201 NM_018518.5 ENSP00000367986 P4Q7L590-2
MCM10ENST00000484800.6 linkuse as main transcriptc.1621A>T p.Thr541Ser missense_variant 12/201 ENSP00000418268 A1Q7L590-1
MCM10ENST00000378694.1 linkuse as main transcriptc.1618A>T p.Thr540Ser missense_variant 11/185 ENSP00000367966

Frequencies

GnomAD3 genomes
AF:
0.122
AC:
18592
AN:
152012
Hom.:
1392
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0833
Gnomad AMI
AF:
0.0570
Gnomad AMR
AF:
0.0679
Gnomad ASJ
AF:
0.0579
Gnomad EAS
AF:
0.0231
Gnomad SAS
AF:
0.0374
Gnomad FIN
AF:
0.223
Gnomad MID
AF:
0.0348
Gnomad NFE
AF:
0.162
Gnomad OTH
AF:
0.0868
GnomAD3 exomes
AF:
0.115
AC:
28832
AN:
251270
Hom.:
2295
AF XY:
0.114
AC XY:
15510
AN XY:
135790
show subpopulations
Gnomad AFR exome
AF:
0.0819
Gnomad AMR exome
AF:
0.0467
Gnomad ASJ exome
AF:
0.0525
Gnomad EAS exome
AF:
0.0264
Gnomad SAS exome
AF:
0.0418
Gnomad FIN exome
AF:
0.225
Gnomad NFE exome
AF:
0.159
Gnomad OTH exome
AF:
0.113
GnomAD4 exome
AF:
0.144
AC:
210785
AN:
1461496
Hom.:
17113
Cov.:
32
AF XY:
0.141
AC XY:
102822
AN XY:
727084
show subpopulations
Gnomad4 AFR exome
AF:
0.0798
Gnomad4 AMR exome
AF:
0.0493
Gnomad4 ASJ exome
AF:
0.0521
Gnomad4 EAS exome
AF:
0.0225
Gnomad4 SAS exome
AF:
0.0417
Gnomad4 FIN exome
AF:
0.220
Gnomad4 NFE exome
AF:
0.163
Gnomad4 OTH exome
AF:
0.118
GnomAD4 genome
AF:
0.122
AC:
18610
AN:
152130
Hom.:
1393
Cov.:
32
AF XY:
0.121
AC XY:
9030
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.0834
Gnomad4 AMR
AF:
0.0677
Gnomad4 ASJ
AF:
0.0579
Gnomad4 EAS
AF:
0.0234
Gnomad4 SAS
AF:
0.0374
Gnomad4 FIN
AF:
0.223
Gnomad4 NFE
AF:
0.162
Gnomad4 OTH
AF:
0.0859
Alfa
AF:
0.144
Hom.:
1377
Bravo
AF:
0.108
TwinsUK
AF:
0.163
AC:
606
ALSPAC
AF:
0.159
AC:
614
ESP6500AA
AF:
0.0881
AC:
388
ESP6500EA
AF:
0.146
AC:
1258
ExAC
AF:
0.118
AC:
14272
Asia WGS
AF:
0.0380
AC:
132
AN:
3478
EpiCase
AF:
0.141
EpiControl
AF:
0.139

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.093
BayesDel_addAF
Benign
-0.78
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
3.0
DANN
Benign
0.29
DEOGEN2
Benign
0.030
.;T;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.34
N
LIST_S2
Benign
0.35
T;T;T
MetaRNN
Benign
0.0028
T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
1.1
.;L;.
MutationTaster
Benign
1.0
P;P;P;P
PrimateAI
Benign
0.33
T
PROVEAN
Benign
0.080
N;N;N
REVEL
Benign
0.085
Sift
Benign
0.65
T;T;T
Sift4G
Benign
0.44
T;T;T
Polyphen
0.0020
B;B;B
Vest4
0.020
MPC
0.091
ClinPred
0.0011
T
GERP RS
4.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.026
gMVP
0.080

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs7905784; hg19: chr10-13234356; COSMIC: COSV66334815; COSMIC: COSV66334815; API