rs2268855

Positions:

• chr6-52269703-A-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCM3	NM_002388.6	c.1828-477T>A		intron_variant		ENST00000596288.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCM3	ENST00000596288.7	c.1828-477T>A		intron_variant		1	NM_002388.6	P1

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

Gnomad4 AFR AF: 0.715

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.622

Gnomad4 EAS AF: 0.667

Gnomad4 SAS AF: 0.700

Gnomad4 FIN AF: 0.636

Gnomad4 NFE AF: 0.621

Gnomad4 OTH AF: 0.635

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.7
DANN	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs2268855; hg19: chr6-52134501;