MCM5 p.Thr180Ser

Variant names:

• chr22-35406667-A-T
• NM_006739.4:c.538A>T
• MCM5 p.Thr180Ser

Your query was ambiguous. Multiple possible variants found:

• chr22-35406667-A-T
• chr22-35406668-C-G
• chr22-35406667-ACC-TCT
• chr22-35406667-ACC-TCA
• chr22-35406667-ACC-TCG
• chr22-35406668-CC-GT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006739.4(MCM5):​c.538A>T​(p.Thr180Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MCM5 NM_006739.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.30
• Publications: 0 publications found

Genes affected

MCM5 (HGNC:6948): (minichromosome maintenance complex component 5) The protein encoded by this gene is structurally very similar to the CDC46 protein from S. cerevisiae, a protein involved in the initiation of DNA replication. The encoded protein is a member of the MCM family of chromatin-binding proteins and can interact with at least two other members of this family. The encoded protein is upregulated in the transition from the G0 to G1/S phase of the cell cycle and may actively participate in cell cycle regulation. [provided by RefSeq, Jul 2008]

MCM5 Gene-Disease associations (from GenCC):

• Meier-Gorlin syndrome 8

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.068390995).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006739.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCM5	NM_006739.4	MANE Select	c.538A>T	p.Thr180Ser	missense	Exon 5 of 17	NP_006730.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCM5	ENST00000216122.9	TSL:1 MANE Select	c.538A>T	p.Thr180Ser	missense	Exon 5 of 17	ENSP00000216122.3	P33992
	MCM5	ENST00000917548.1		c.538A>T	p.Thr180Ser	missense	Exon 5 of 17	ENSP00000587607.1
	MCM5	ENST00000917543.1		c.538A>T	p.Thr180Ser	missense	Exon 5 of 18	ENSP00000587602.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.043	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.0	N
PhyloP100		2.3
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.12	N
REVEL	Benign	0.090
Sift	Benign	0.75	T
Sift4G	Benign	0.75	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.037
gMVP		0.13
Mutation Taster		=99/1	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr22-35802660;