chr6-52282511-A-C

Position:

• chr6-52282511-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002388.6(MCM3):​c.400+142T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 693,420 control chromosomes in the GnomAD database, including 9,781 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 0.17 (2784 hom., cov: 32)
  • Exomes 𝑓: 0.14 (6997 hom.)
• Consequence: MCM3 NM_002388.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.793

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCM3	NM_002388.6	c.400+142T>G		intron_variant		ENST00000596288.7	NP_002379.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCM3	ENST00000596288.7	c.400+142T>G		intron_variant		1	NM_002388.6	ENSP00000472940	P1
MCM3	ENST00000229854.12	c.430+142T>G		intron_variant		1		ENSP00000229854
MCM3	ENST00000616552.4	c.535+142T>G		intron_variant		1		ENSP00000480987
MCM3	ENST00000419835.8	c.262+142T>G		intron_variant		2		ENSP00000388647

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25693 AN: 151942 Hom.: 2774 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.165

GnomAD4 exome AF: 0.139 AC: 75380 AN: 541360 Hom.: 6997 AF XY: 0.138 AC XY: 39308 AN XY: 284738

Gnomad4 AFR exome AF: 0.277

Gnomad4 AMR exome AF: 0.136

Gnomad4 ASJ exome AF: 0.100

Gnomad4 EAS exome AF: 0.408

Gnomad4 SAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.165

Gnomad4 NFE exome AF: 0.103

Gnomad4 OTH exome AF: 0.148

GnomAD4 genome AF: 0.169 AC: 25735 AN: 152060 Hom.: 2784 Cov.: 32 AF XY: 0.172 AC XY: 12810 AN XY: 74312

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.428

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.100

Gnomad4 OTH AF: 0.164

Alfa AF: 0.110 Hom.: 1365

Bravo AF: 0.175

Asia WGS AF: 0.269 AC: 936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.21
DANN	Benign	0.32

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

Publications

LitVar

Other links and lift over

dbSNP: rs7774976; hg19: chr6-52147309;