Variant 6-118814970-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_017696.3(MCM9):c.3286A>G(p.Met1096Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00333 in 1,550,440 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0035 ( 9 hom. )

Consequence

MCM9
NM_017696.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.439

Variant links:

Genes affected

MCM9 (HGNC:21484): (minichromosome maintenance 9 homologous recombination repair factor) The protein encoded by this gene is a member of the mini-chromosome maintenance (MCM) protein family that are essential for the initiation of eukaryotic genome replication. Binding of this protein to chromatin has been shown to be a pre-requisite for recruiting the MCM2-7 helicase to DNA replication origins. This protein also binds, and is a positive regulator of, the chromatin licensing and DNA replication factor 1, CDT1. [provided by RefSeq, Nov 2010]

MCM9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004646033).

BP6

Variant 6-118814970-T-C is Benign according to our data. Variant chr6-118814970-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 774185.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCM9	NM_017696.3 linkuse as main transcript	c.3286A>G	p.Met1096Val	missense_variant	14/14	ENST00000619706.5	NP_060166.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCM9	ENST00000619706.5 linkuse as main transcript	c.3286A>G	p.Met1096Val	missense_variant	14/14	5	NM_017696.3	ENSP00000480469	P1	Q9NXL9-1
MCM9	ENST00000316316.10 linkuse as main transcript	c.3286A>G	p.Met1096Val	missense_variant	13/13	5		ENSP00000314505	P1	Q9NXL9-1

Frequencies

GnomAD3 genomes

AF:

0.00211

AC:

321

AN:

152020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000435

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000624

Gnomad FIN

AF:

0.00519

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00325

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00240

AC:

358

AN:

149360

Hom.:

AF XY:

0.00233

AC XY:

187

AN XY:

80254

show subpopulations

Gnomad AFR exome

AF:

0.000291

Gnomad AMR exome

AF:

0.000814

Gnomad ASJ exome

AF:

0.000359

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000754

Gnomad FIN exome

AF:

0.00730

Gnomad NFE exome

AF:

0.00330

Gnomad OTH exome

AF:

0.00255

GnomAD4 exome

AF:

0.00347

AC:

4848

AN:

1398302

Hom.:

Cov.:

AF XY:

0.00334

AC XY:

2304

AN XY:

689668

show subpopulations

Gnomad4 AFR exome

AF:

0.000285

Gnomad4 AMR exome

AF:

0.000924

Gnomad4 ASJ exome

AF:

0.000477

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000959

Gnomad4 FIN exome

AF:

0.00797

Gnomad4 NFE exome

AF:

0.00389

Gnomad4 OTH exome

AF:

0.00234

GnomAD4 genome

AF:

0.00211

AC:

321

AN:

152138

Hom.:

Cov.:

AF XY:

0.00210

AC XY:

156

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000624

Gnomad4 FIN

AF:

0.00519

Gnomad4 NFE

AF:

0.00325

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00300

Hom.:

Bravo

AF:

0.00193

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00259

AC:

ExAC

AF:

0.00178

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MCM9-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 16, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.017

DANN

Benign

0.33

DEOGEN2

Benign

0.033

T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0090

LIST_S2

Benign

0.25

.;T

M_CAP

Benign

0.0032

MetaRNN

Benign

0.0046

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.20

N;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.23

PROVEAN

Benign

0.36

N;.

REVEL

Benign

0.0010

Sift

Benign

0.23

T;.

Sift4G

Benign

0.48

T;T

Polyphen

0.0

B;B

Vest4

0.031

MVP

0.16

MPC

0.12

ClinPred

0.0015

GERP RS

-1.8

Varity_R

0.047

gMVP

0.061

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over