Genetic Variant NM_005916.5:c.1616A>T (chr7-100095450-T-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM2PM5BP4

The NM_005916.5(MCM7):c.1616A>T(p.Tyr539Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y539C) has been classified as Pathogenic.

Frequency

Genomes: not found (cov: 34)

Consequence

MCM7
NM_005916.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.67

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:

Genome browser will be placed here

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;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr7-100095450-T-C is described in ClinVar as Pathogenic. ClinVar VariationId is 1173058.Status of the report is criteria_provided_single_submitter, 1 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.34047312).

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.1616A>T	p.Tyr539Phe	missense	Exon 12 of 15	NP_005907.3
MCM7	NM_001439271.1		c.1295A>T	p.Tyr432Phe	missense	Exon 12 of 15	NP_001426200.1
MCM7	NM_001439272.1		c.1295A>T	p.Tyr432Phe	missense	Exon 12 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.1616A>T	p.Tyr539Phe	missense	Exon 12 of 15	ENSP00000307288.5	P33993-1
MCM7	ENST00000343023.10	TSL:1	c.986-2334A>T		intron	N/A	ENSP00000344006.6	P33993-2
MCM7	ENST00000489841.6	TSL:1	n.2337A>T		non_coding_transcript_exon	Exon 11 of 14

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.18

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.0071

MetaRNN

Benign

0.34

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

4.7

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.17

Sift

Benign

0.23

Sift4G

Benign

0.39

Polyphen

0.33

Vest4

0.47

MutPred

0.51

Loss of phosphorylation at Y539 (P = 0.0337)

MVP

0.38

MPC

0.20

ClinPred

0.84

GERP RS

6.2

Varity_R

0.53

gMVP

0.40

Mutation Taster

=56/44

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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