Variant rs7774976 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.793

Variant links:

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]

MCM3 links:

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ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.400+142T>G		intron_variant		ENST00000596288.7	NP_002379.4

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
MCM3	ENST00000596288.7 linkuse as main transcript	c.400+142T>G	intron_variant	1	NM_002388.6	ENSP00000472940	P1	P25205-1
MCM3	ENST00000229854.12 linkuse as main transcript	c.430+142T>G	intron_variant	1		ENSP00000229854
MCM3	ENST00000616552.4 linkuse as main transcript	c.535+142T>G	intron_variant	1		ENSP00000480987		P25205-2
MCM3	ENST00000419835.8 linkuse as main transcript	c.262+142T>G	intron_variant	2		ENSP00000388647

Frequencies

GnomAD3 genomes

AF:

0.169

AC:

25693

AN:

151942

Hom.:

2774

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.172

AC XY:

12810

AN XY:

74312

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over