Variant 6-118814936-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_017696.3(MCM9):c.3320G>A(p.Arg1107His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,535,830 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000034 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

MCM9
NM_017696.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.793

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.045567364).

BP6

Variant 6-118814936-C-T is Benign according to our data. Variant chr6-118814936-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2245333.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCM9	NM_017696.3 linkuse as main transcript	c.3320G>A	p.Arg1107His	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.3320G>A	p.Arg1107His	missense_variant	14/14	5	NM_017696.3	ENSP00000480469	P1	Q9NXL9-1
MCM9	ENST00000316316.10 linkuse as main transcript	c.3320G>A	p.Arg1107His	missense_variant	13/13	5		ENSP00000314505	P1	Q9NXL9-1

Frequencies

GnomAD3 genomes

AF:

0.0000335

AC:

AN:

149110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000989

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000684

AC:

AN:

146218

Hom.:

AF XY:

0.0000127

AC XY:

AN XY:

78802

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000449

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1386720

Hom.:

Cov.:

AF XY:

0.0000102

AC XY:

AN XY:

683966

show subpopulations

Gnomad4 AFR exome

AF:

0.0000323

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000574

Gnomad4 SAS exome

AF:

0.0000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000103

Gnomad4 OTH exome

AF:

0.0000348

GnomAD4 genome

AF:

0.0000335

AC:

AN:

149110

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

72602

show subpopulations

Gnomad4 AFR

AF:

0.0000989

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000149

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000480

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.83

CADD

Benign

8.3

DANN

Benign

0.88

DEOGEN2

Benign

0.040

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0037

LIST_S2

Benign

0.21

.;T

M_CAP

Benign

0.0061

MetaRNN

Benign

0.046

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.34

N;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.22

PROVEAN

Benign

0.37

N;.

REVEL

Benign

0.028

Sift

Benign

0.26

T;.

Sift4G

Benign

0.11

T;T

Polyphen

0.0

B;B

Vest4

0.021

MutPred

0.49

Loss of MoRF binding (P = 0.0329);Loss of MoRF binding (P = 0.0329);

MVP

0.048

MPC

0.15

ClinPred

0.053

GERP RS

-4.9

Varity_R

0.021

gMVP

0.053

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