Variant rs16991615 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_032485.6(MCM8):c.1021G>A(p.Glu341Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0559 in 1,610,584 control chromosomes in the GnomAD database, including 2,815 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.041 ( 182 hom., cov: 32)

Exomes 𝑓: 0.057 ( 2633 hom. )

Consequence

MCM8
NM_032485.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.99

Variant links:

Genes affected

MCM8 (HGNC:16147): (minichromosome maintenance 8 homologous recombination repair factor) The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the initiation of eukaryotic genome replication. The hexameric protein complex formed by the mini-chromosome maintenance proteins is a key component of the pre-replication complex and may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. This protein contains the central domain that is conserved among the mini-chromosome maintenance proteins. The encoded protein may interact with other mini-chromosome maintenance proteins and play a role in DNA replication. This gene may be associated with length of reproductive lifespan and menopause. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2013]

MCM8 links:

ENSG00000286235 (HGNC:):

ENSG00000286235 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 (MetaRNN=0.0018333793).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCM8	NM_032485.6 linkuse as main transcript	c.1021G>A	p.Glu341Lys	missense_variant	9/19	ENST00000610722.4	NP_115874.3	Q9UJA3-1B4DN82

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCM8	ENST00000610722.4 linkuse as main transcript	c.1021G>A	p.Glu341Lys	missense_variant	9/19	1	NM_032485.6	ENSP00000478141.1		Q9UJA3-1
ENSG00000286235	ENST00000652720.1 linkuse as main transcript	c.1021G>A	p.Glu341Lys	missense_variant	9/24			ENSP00000498784.1		A0A494C100

Frequencies

GnomAD3 genomes

AF:

0.0414

AC:

6297

AN:

152174

Hom.:

182

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0109

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.0565

Gnomad ASJ

AF:

0.101

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0215

Gnomad FIN

AF:

0.0170

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0614

Gnomad OTH

AF:

0.0602

GnomAD3 exomes

AF:

0.0451

AC:

11287

AN:

250206

Hom.:

341

AF XY:

0.0463

AC XY:

6256

AN XY:

135174

show subpopulations

Gnomad AFR exome

AF:

0.00936

Gnomad AMR exome

AF:

0.0389

Gnomad ASJ exome

AF:

0.103

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0250

Gnomad FIN exome

AF:

0.0203

Gnomad NFE exome

AF:

0.0637

Gnomad OTH exome

AF:

0.0585

GnomAD4 exome

AF:

0.0574

AC:

83700

AN:

1458292

Hom.:

2633

Cov.:

AF XY:

0.0567

AC XY:

41108

AN XY:

724802

show subpopulations

Gnomad4 AFR exome

AF:

0.00841

Gnomad4 AMR exome

AF:

0.0391

Gnomad4 ASJ exome

AF:

0.108

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.0268

Gnomad4 FIN exome

AF:

0.0204

Gnomad4 NFE exome

AF:

0.0648

Gnomad4 OTH exome

AF:

0.0547

GnomAD4 genome

AF:

0.0414

AC:

6298

AN:

152292

Hom.:

182

Cov.:

AF XY:

0.0398

AC XY:

2965

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0109

Gnomad4 AMR

AF:

0.0564

Gnomad4 ASJ

AF:

0.101

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0218

Gnomad4 FIN

AF:

0.0170

Gnomad4 NFE

AF:

0.0614

Gnomad4 OTH

AF:

0.0595

Alfa

AF:

0.0608

Hom.:

709

Bravo

AF:

0.0436

TwinsUK

AF:

0.0601

AC:

223

ALSPAC

AF:

0.0612

AC:

236

ESP6500AA

AF:

0.0120

AC:

ESP6500EA

AF:

0.0692

AC:

595

ExAC

AF:

0.0450

AC:

5461

Asia WGS

AF:

0.00895

AC:

AN:

3478

EpiCase

AF:

0.0637

EpiControl

AF:

0.0682

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.041

.;T;.;T;.

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.012

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

D;D;D;.;T

MetaRNN

Benign

0.0018

T;T;T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.97

L;L;L;L;L

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.9

N;N;N;.;N

REVEL

Benign

0.048

Sift

Benign

0.19

T;T;T;.;T

Sift4G

Benign

0.17

T;T;T;T;T

Polyphen

0.32

B;B;.;B;B

Vest4

0.34

MPC

0.25

ClinPred

0.017

GERP RS

5.0

Varity_R

0.10

gMVP

0.54

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