rs133425

Variant names:

• chr22-35418969-C-G
• rs133425
• NM_006739.4:c.1704-915C>G

Your query was ambiguous. Multiple possible variants found:

• chr22-35418969-C-G
• chr22-35418969-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006739.4(MCM5):​c.1704-915C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,210 control chromosomes in the GnomAD database, including 1,275 homozygotes. 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 0.11 (1275 hom., cov: 32)
• Consequence: MCM5 NM_006739.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

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.1704-915C>G		intron	N/A	NP_006730.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCM5	ENST00000216122.9	TSL:1 MANE Select	c.1704-915C>G		intron	N/A	ENSP00000216122.3	P33992
	MCM5	ENST00000917548.1		c.1704-915C>G		intron	N/A	ENSP00000587607.1
	MCM5	ENST00000917543.1		c.1734-915C>G		intron	N/A	ENSP00000587602.1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17270 AN: 152092 Hom.: 1255 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0741

Gnomad ASJ AF: 0.0550

Gnomad EAS AF: 0.0490

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.0891

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0778

Gnomad OTH AF: 0.112

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.114 AC: 17335 AN: 152210 Hom.: 1275 Cov.: 32 AF XY: 0.114 AC XY: 8466 AN XY: 74416

African (AFR) AF: 0.204 AC: 8449 AN: 41502

American (AMR) AF: 0.0741 AC: 1133 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0550 AC: 191 AN: 3470

East Asian (EAS) AF: 0.0493 AC: 255 AN: 5172

South Asian (SAS) AF: 0.163 AC: 786 AN: 4822

European-Finnish (FIN) AF: 0.0891 AC: 945 AN: 10608

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0778 AC: 5292 AN: 68018

Other (OTH) AF: 0.111 AC: 235 AN: 2112

Alfa AF: 0.0314 Hom.: 21

Bravo AF: 0.113

Asia WGS AF: 0.101 AC: 350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.4
DANN	Benign	0.68
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs133425; hg19: chr22-35814962;