NM_005916.5:c.1773G>C

Variant names:

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005916.5(MCM7):c.1773G>C(p.Glu591Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0031 in 1,614,204 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0032 ( 8 hom. )

Consequence

MCM7
NM_005916.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.78

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:

MIR106B (HGNC:31495): (microRNA 106b) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR106B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011098564).

BP6

Variant 7-100094248-C-G is Benign according to our data. Variant chr7-100094248-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 774658.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 322 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCM7	NM_005916.5 link	c.1773G>C	p.Glu591Asp	missense_variant	Exon 13 of 15	ENST00000303887.10	NP_005907.3	P33993-1C6EMX8A0A0S2Z4A5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCM7	ENST00000303887.10 link	c.1773G>C	p.Glu591Asp	missense_variant	Exon 13 of 15	1	NM_005916.5	ENSP00000307288.5		P33993-1

Frequencies

GnomAD3 genomes

AF:

0.00212

AC:

322

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00347

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00315

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00199

AC:

501

AN:

251480

Hom.:

AF XY:

0.00198

AC XY:

269

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00162

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.000601

Gnomad NFE exome

AF:

0.00349

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00320

AC:

4684

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00312

AC XY:

2269

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.00181

Gnomad4 ASJ exome

AF:

0.00161

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.000786

Gnomad4 NFE exome

AF:

0.00387

Gnomad4 OTH exome

AF:

0.00316

GnomAD4 genome

AF:

0.00211

AC:

322

AN:

152314

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

145

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000746

Gnomad4 AMR

AF:

0.00346

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000942

Gnomad4 NFE

AF:

0.00315

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00252

Hom.:

Bravo

AF:

0.00234

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00337

AC:

ExAC

AF:

0.00210

AC:

255

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MCM7-related disorder

Benign:1

May 25, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

May 11, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.045

.;.;T

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.29

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;.;D

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.59

.;.;N

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.75

N;.;N

REVEL

Benign

0.21

Sift

Benign

0.54

T;.;T

Sift4G

Benign

0.37

T;T;T

Polyphen

0.0080

.;.;B

Vest4

0.74

MutPred

0.53

.;.;Loss of catalytic residue at W593 (P = 0.0318);

MVP

0.22

MPC

0.14

ClinPred

0.0074

GERP RS

2.2

Varity_R

0.26

gMVP

0.44

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over