rs7774976

Variant names:

• chr6-52282511-A-C
• rs7774976
• NM_002388.6:c.400+142T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-52282511-A-C
• chr6-52282511-A-G
• chr6-52282511-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.92).
• 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 rank	MANE	Protein	UniProt
MCM3	NM_002388.6	c.400+142T>G		intron_variant	Intron 3 of 16	ENST00000596288.7	NP_002379.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCM3	ENST00000596288.7	c.400+142T>G		intron_variant	Intron 3 of 16	1	NM_002388.6	ENSP00000472940.2
MCM3	ENST00000616552.4	c.535+142T>G		intron_variant	Intron 3 of 16	1		ENSP00000480987.1
MCM3	ENST00000229854.12	c.430+142T>G		intron_variant	Intron 2 of 15	1		ENSP00000229854.6
MCM3	ENST00000419835.8	c.262+142T>G		intron_variant	Intron 2 of 15	2		ENSP00000388647.4

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

African (AFR) AF: 0.277 AC: 4072 AN: 14690

American (AMR) AF: 0.136 AC: 3402 AN: 25078

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 1520 AN: 15144

East Asian (EAS) AF: 0.408 AC: 12946 AN: 31768

South Asian (SAS) AF: 0.154 AC: 7754 AN: 50480

European-Finnish (FIN) AF: 0.165 AC: 7174 AN: 43432

Middle Eastern (MID) AF: 0.152 AC: 329 AN: 2168

European-Non Finnish (NFE) AF: 0.103 AC: 33869 AN: 329520

Other (OTH) AF: 0.148 AC: 4314 AN: 29080

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

African (AFR) AF: 0.270 AC: 11184 AN: 41468

American (AMR) AF: 0.144 AC: 2200 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 368 AN: 3468

East Asian (EAS) AF: 0.428 AC: 2212 AN: 5170

South Asian (SAS) AF: 0.150 AC: 720 AN: 4810

European-Finnish (FIN) AF: 0.175 AC: 1849 AN: 10562

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.100 AC: 6800 AN: 67984

Other (OTH) AF: 0.164 AC: 346 AN: 2108

Alfa AF: 0.129 Hom.: 3171

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
PhyloP100		-0.79
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: rs7774976; hg19: chr6-52147309;