rs2268855

Variant names:

• chr6-52269703-A-T
• rs2268855
• NM_002388.6:c.1828-477T>A

Variant summary

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

The NM_002388.6(MCM3):​c.1828-477T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 152,080 control chromosomes in the GnomAD database, including 31,510 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 0.64 (31510 hom., cov: 32)
• Consequence: MCM3 NM_002388.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213
• Publications: 4 publications found

Genes affected

MCM3 (HGNC:6945): (minichromosome maintenance complex component 3) The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are involved in the initiation of eukaryotic genome replication. The hexameric protein complex formed by 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. This protein is a subunit of the protein complex that consists of MCM2-7. It has been shown to interact directly with MCM5/CDC46. This protein also interacts with and is acetylated by MCM3AP, a chromatin-associated acetyltransferase. The acetylation of this protein inhibits the initiation of DNA replication and cell cycle progression. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2018]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002388.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCM3	NM_002388.6	MANE Select	c.1828-477T>A		intron	N/A	NP_002379.4
	MCM3	NM_001366369.2		c.1828-477T>A		intron	N/A	NP_001353298.1
	MCM3	NM_001366370.2		c.1879-477T>A		intron	N/A	NP_001353299.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCM3	ENST00000596288.7	TSL:1 MANE Select	c.1828-477T>A		intron	N/A	ENSP00000472940.2
	MCM3	ENST00000616552.4	TSL:1	c.1963-477T>A		intron	N/A	ENSP00000480987.1
	MCM3	ENST00000229854.12	TSL:1	c.1858-477T>A		intron	N/A	ENSP00000229854.6

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97412 AN: 151962 Hom.: 31491 Cov.: 32

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.635

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

GnomAD4 genome AF: 0.641 AC: 97482 AN: 152080 Hom.: 31510 Cov.: 32 AF XY: 0.641 AC XY: 47676 AN XY: 74350

African (AFR) AF: 0.715 AC: 29679 AN: 41492

American (AMR) AF: 0.507 AC: 7740 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 2156 AN: 3466

East Asian (EAS) AF: 0.667 AC: 3448 AN: 5172

South Asian (SAS) AF: 0.700 AC: 3369 AN: 4816

European-Finnish (FIN) AF: 0.636 AC: 6720 AN: 10562

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.621 AC: 42213 AN: 67976

Other (OTH) AF: 0.635 AC: 1341 AN: 2112

Alfa AF: 0.621 Hom.: 3632

Bravo AF: 0.635

Asia WGS AF: 0.634 AC: 2204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.7
DANN	Benign	0.40
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2268855; hg19: chr6-52134501;