chr6-52276714-T-C

Variant names:

• chr6-52276714-T-C
• rs3765447
• NM_002388.6:c.1166-238A>G

Variant summary

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

The NM_002388.6(MCM3):​c.1166-238A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0605 in 152,176 control chromosomes in the GnomAD database, including 352 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 0.060 (352 hom., cov: 32)
• Consequence: MCM3 NM_002388.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.346
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.121 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCM3	NM_002388.6	MANE Select	c.1166-238A>G		intron	N/A	NP_002379.4
	MCM3	NM_001366369.2		c.1166-238A>G		intron	N/A	NP_001353298.1	A0A0S2Z492
	MCM3	NM_001366370.2		c.1166-238A>G		intron	N/A	NP_001353299.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCM3	ENST00000596288.7	TSL:1 MANE Select	c.1166-238A>G		intron	N/A	ENSP00000472940.2	P25205-1
	MCM3	ENST00000616552.4	TSL:1	c.1301-238A>G		intron	N/A	ENSP00000480987.1	P25205-2
	MCM3	ENST00000229854.12	TSL:1	c.1196-238A>G		intron	N/A	ENSP00000229854.6	A0A499FHX9

Frequencies

GnomAD3 genomes AF: 0.0606 AC: 9207 AN: 152056 Hom.: 353 Cov.: 32

Gnomad AFR AF: 0.0216

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0591

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.0665

Gnomad FIN AF: 0.0479

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0771

Gnomad OTH AF: 0.0703

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

GnomAD4 genome AF: 0.0605 AC: 9202 AN: 152176 Hom.: 352 Cov.: 32 AF XY: 0.0602 AC XY: 4480 AN XY: 74418

African (AFR) AF: 0.0216 AC: 896 AN: 41526

American (AMR) AF: 0.0590 AC: 902 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 439 AN: 3470

East Asian (EAS) AF: 0.130 AC: 670 AN: 5170

South Asian (SAS) AF: 0.0661 AC: 318 AN: 4810

European-Finnish (FIN) AF: 0.0479 AC: 507 AN: 10594

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0771 AC: 5244 AN: 67998

Other (OTH) AF: 0.0710 AC: 150 AN: 2114

Alfa AF: 0.0750 Hom.: 884

Bravo AF: 0.0597

Asia WGS AF: 0.109 AC: 380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.52
DANN	Benign	0.67
PhyloP100		-0.35
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: rs3765447; hg19: chr6-52141512;