Variant 6-118815438-G-T 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.2818C>A(p.His940Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000751 in 1,550,452 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0038 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 5 hom. )

Consequence

MCM9
NM_017696.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.532

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=0.0045559704).

BP6

Variant 6-118815438-G-T is Benign according to our data. Variant chr6-118815438-G-T is described in ClinVar as [Benign]. Clinvar id is 733900.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCM9	NM_017696.3 linkuse as main transcript	c.2818C>A	p.His940Asn	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.2818C>A	p.His940Asn	missense_variant	14/14	5	NM_017696.3	ENSP00000480469	P1	Q9NXL9-1
MCM9	ENST00000316316.10 linkuse as main transcript	c.2818C>A	p.His940Asn	missense_variant	13/13	5		ENSP00000314505	P1	Q9NXL9-1

Frequencies

GnomAD3 genomes

AF:

0.00381

AC:

579

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0134

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00336

GnomAD3 exomes

AF:

0.000814

AC:

121

AN:

148718

Hom.:

AF XY:

0.000787

AC XY:

AN XY:

80046

show subpopulations

Gnomad AFR exome

AF:

0.0154

Gnomad AMR exome

AF:

0.000652

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000233

GnomAD4 exome

AF:

0.000416

AC:

582

AN:

1398222

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

259

AN XY:

689604

show subpopulations

Gnomad4 AFR exome

AF:

0.0156

Gnomad4 AMR exome

AF:

0.000897

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000631

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000463

Gnomad4 OTH exome

AF:

0.000776

GnomAD4 genome

AF:

0.00383

AC:

583

AN:

152230

Hom.:

Cov.:

AF XY:

0.00363

AC XY:

270

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0134

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00210

Hom.:

Bravo

AF:

0.00450

ExAC

AF:

0.000865

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.73

CADD

Benign

1.3

DANN

Benign

0.28

DEOGEN2

Benign

0.042

T;T

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.36

.;T

MetaRNN

Benign

0.0046

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.0

L;L

MutationTaster

Benign

1.0

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.30

N;.

REVEL

Benign

0.065

Sift

Benign

0.73

T;.

Sift4G

Benign

0.58

T;T

Polyphen

0.45

P;P

Vest4

0.064

MVP

0.25

MPC

0.13

ClinPred

0.0047

GERP RS

3.2

Varity_R

0.040

gMVP

0.076

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