chr7-100092988-C-G

Position:

• chr7-100092988-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.03

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.745

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCM7	NM_005916.5	c.2104G>C	p.Glu702Gln	missense_variant	15/15	ENST00000303887.10
MCM7	NM_001278595.2	c.1576G>C	p.Glu526Gln	missense_variant	14/14
MCM7	NM_182776.3	c.1576G>C	p.Glu526Gln	missense_variant	14/14
MCM7	XM_005250348.4	c.1783G>C	p.Glu595Gln	missense_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCM7	ENST00000303887.10	c.2104G>C	p.Glu702Gln	missense_variant	15/15	1	NM_005916.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.2104G>C (p.E702Q) alteration is located in exon 15 (coding exon 15) of the MCM7 gene. This alteration results from a G to C substitution at nucleotide position 2104, causing the glutamic acid (E) at amino acid position 702 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	.;.;.;T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;.;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.75	D;D;D;D
MetaSVM	Benign	-0.49	T
MutationAssessor	Pathogenic	3.1	.;.;.;M
MutationTaster	Benign	0.80	D;D;D
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-2.1	N;.;N;N
REVEL	Benign	0.25
Sift	Benign	0.31	T;.;D;T
Sift4G	Benign	0.29	T;T;D;T
Polyphen		1.0	.;.;.;D
Vest4		0.63
MutPred		0.37		.;.;.;Loss of helix (P = 0.1706);
MVP		0.87
MPC		0.60
ClinPred		0.98	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.59

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: rs1180646503; hg19: chr7-99690611;