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

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_017696.3(MCM9):c.3320G>C(p.Arg1107Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000037 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MCM9
NM_017696.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U: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:

MCM9 (HGNC:):

MCM9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.053210735).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCM9	NM_017696.3 linkuse as main transcript	c.3320G>C	p.Arg1107Pro	missense_variant	14/14	ENST00000619706.5	NP_060166.2	Q9NXL9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCM9	ENST00000619706.5 linkuse as main transcript	c.3320G>C	p.Arg1107Pro	missense_variant	14/14	5	NM_017696.3	ENSP00000480469.1		Q9NXL9-1
MCM9	ENST00000316316.10 linkuse as main transcript	c.3320G>C	p.Arg1107Pro	missense_variant	13/13	5		ENSP00000314505.5		Q9NXL9-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

149108

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000103

AC:

AN:

146218

Hom.:

AF XY:

0.000102

AC XY:

AN XY:

78802

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000209

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:

0.000149

Gnomad OTH exome

AF:

0.000238

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000368

AC:

AN:

1386004

Hom.:

Cov.:

AF XY:

0.0000395

AC XY:

AN XY:

683596

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000318

Gnomad4 ASJ exome

AF:

0.000121

Gnomad4 EAS exome

AF:

0.0000575

Gnomad4 SAS exome

AF:

0.0000513

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000271

Gnomad4 OTH exome

AF:

0.0000348

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

149108

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72602

Gnomad4 AFR

AF:

0.00

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2024

The c.3320G>C (p.R1107P) alteration is located in exon 12 (coding exon 12) of the MCM9 gene. This alteration results from a G to C substitution at nucleotide position 3320, causing the arginine (R) at amino acid position 1107 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.78

DANN

Benign

0.88

DEOGEN2

Benign

0.044

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.32

.;T

M_CAP

Benign

0.0095

MetaRNN

Benign

0.053

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.34

N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.21

N;.

REVEL

Benign

0.024

Sift

Benign

0.23

T;.

Sift4G

Benign

0.23

T;T

Polyphen

0.054

B;B

Vest4

0.10

MutPred

0.47

Loss of MoRF binding (P = 0.0094);Loss of MoRF binding (P = 0.0094);

MVP

0.11

MPC

0.21

ClinPred

0.038

GERP RS

-4.9

Varity_R

0.091

gMVP

0.073

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