Genetic Variant NM_005916.5:c.2104G>C (chr7-100092988-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_005916.5(MCM7):c.2104G>C(p.Glu702Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

MCM7
NM_005916.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.03

Publications

0 publications found

Variant links:

Genes affected

MCM7 (HGNC:6950): (minichromosome maintenance complex component 7) The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the initiation of eukaryotic genome replication. The hexameric protein complex formed by the MCM proteins is a key component of the pre-replication complex (pre_RC) and may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. The MCM complex consisting of this protein and MCM2, 4 and 6 proteins possesses DNA helicase activity, and may act as a DNA unwinding enzyme. Cyclin D1-dependent kinase, CDK4, is found to associate with this protein, and may regulate the binding of this protein with the tumorsuppressor protein RB1/RB. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

MCM7 links:

COPS6 (HGNC:21749): (COP9 signalosome subunit 6) The protein encoded by this gene is one of the eight subunits of COP9 signalosome, a highly conserved protein complex that functions as an important regulator in multiple signaling pathways. The structure and function of COP9 signalosome is similar to that of the 19S regulatory particle of 26S proteasome. COP9 signalosome has been shown to interact with SCF-type E3 ubiquitin ligases and act as a positive regulator of E3 ubiquitin ligases. This protein belongs to translation initiation factor 3 (eIF3) superfamily. It is involved in the regulation of cell cycle and likely to be a cellular cofactor for HIV-1 accessory gene product Vpr. [provided by RefSeq, Jul 2008]

COPS6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.745

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005916.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MCM7	NM_005916.5	MANE Select	c.2104G>C	p.Glu702Gln	missense	Exon 15 of 15	NP_005907.3
MCM7	NM_001439271.1		c.1783G>C	p.Glu595Gln	missense	Exon 15 of 15	NP_001426200.1
MCM7	NM_001439272.1		c.1783G>C	p.Glu595Gln	missense	Exon 15 of 15	NP_001426201.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MCM7	ENST00000303887.10	TSL:1 MANE Select	c.2104G>C	p.Glu702Gln	missense	Exon 15 of 15	ENSP00000307288.5	P33993-1
MCM7	ENST00000343023.10	TSL:1	c.1114G>C	p.Glu372Gln	missense	Exon 9 of 9	ENSP00000344006.6	P33993-2
MCM7	ENST00000489841.6	TSL:1	n.2825G>C		non_coding_transcript_exon	Exon 14 of 14

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.040

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.75

MetaSVM

Benign

-0.49

MutationAssessor

Pathogenic

3.1

PhyloP100

7.0

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-2.1

REVEL

Benign

0.25

Sift

Benign

0.31

Sift4G

Benign

0.29

Polyphen

1.0

Vest4

0.63

MutPred

0.37

Loss of helix (P = 0.1706)

MVP

0.87

MPC

0.60

ClinPred

0.98

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.22

gMVP

0.59

Mutation Taster

=36/64

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over