chr7-100093033-G-T

Variant names:

• chr7-100093033-G-T
• rs146568179
• NM_005916.5:c.2059C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005916.5(MCM7):​c.2059C>A​(p.Arg687Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: MCM7 NM_005916.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.12

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3241855).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCM7	NM_005916.5	c.2059C>A	p.Arg687Ser	missense_variant	Exon 15 of 15	ENST00000303887.10	NP_005907.3
MCM7	NM_001278595.2	c.1531C>A	p.Arg511Ser	missense_variant	Exon 14 of 14		NP_001265524.1
MCM7	NM_182776.3	c.1531C>A	p.Arg511Ser	missense_variant	Exon 14 of 14		NP_877577.1
MCM7	XM_005250348.4	c.1738C>A	p.Arg580Ser	missense_variant	Exon 15 of 15		XP_005250405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCM7	ENST00000303887.10	c.2059C>A	p.Arg687Ser	missense_variant	Exon 15 of 15	1	NM_005916.5	ENSP00000307288.5

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152226 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152226 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74368

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.33	.;.;.;T
Eigen	Benign	-0.044
Eigen_PC	Benign	-0.0068
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.97	D;.;D;D
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.32	T;T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.0	.;.;.;M
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-2.2	N;.;N;D
REVEL	Benign	0.18
Sift	Benign	0.049	D;.;D;D
Sift4G	Benign	0.084	T;T;D;T
Polyphen		0.35	.;.;.;B
Vest4		0.48
MutPred		0.51		.;.;.;Gain of glycosylation at R687 (P = 0.0169);
MVP		0.80
MPC		0.28
ClinPred		0.36	T
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.18
gMVP		0.62

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: rs146568179; hg19: chr7-99690656;